Is CXCR4-Targeted 68Ga-Pentixafor PET/CT a Reliable AVS-free Modality for Surgical Decision-making and Prognostic Prediction in Primary Aldosteronism with Bilateral Adrenal Lesions?

Is CXCR4-Targeted 68Ga-Pentixafor PET/CT a Reliable AVS-free Modality for Surgical Decision-making and Prognostic Prediction in Primary Aldosteronism with Bilateral Adrenal Lesions? | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Is CXCR4-Targeted 68 Ga-Pentixafor PET/CT a Reliable AVS-free Modality for Surgical Decision-making and Prognostic Prediction in Primary Aldosteronism with Bilateral Adrenal Lesions? Zhiwei Shu, Yao He, Tingting Long, Min Guo, Zhuying Xia, Xiaodan Fu, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6385295/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 28 Aug, 2025 Read the published version in EJNMMI Research → Version 1 posted 4 You are reading this latest preprint version Abstract Background For patients diagnosed with primary aldosteronism accompanied by bilateral adrenal lesions, identifying optimal candidates for surgical intervention remains a significant clinical challenge. Although adrenal venous sampling (AVS) is currently the gold standard for lateralizing aldosterone hypersecretion, its technical complexity, invasiveness, and interpretive difficulties restrict its widespread adoption. In this study, we aimed to investigate the clinical application of 68 Ga-pentixafor positron emission tomography/computed tomography (PET/CT) as a non-invasive imaging modality in AVS-free surgical decision-making for PA patients with bilateral adrenal lesions. Results Among the 51 patients who underwent 68 Ga-pentixafor PET/CT, 36 patients had adrenalectomy, with the surgical side determined by PET/CT lateralization. The postoperative complete biochemical and clinical success rates for these patients were 91.67% and 100%, respectively, Additionally, receiver operating characteristic curve analysis indicated that PET/CT results were favorable predictors of postoperative outcomes in surgical patients. Postoperative pathological evaluation of 68 Ga-pentixafor PET/CT-guided surgical patients revealed that 86.11% had adrenocortical adenomas with positive CYP11B2 and CXCR4 expression. Conclusion CXCR4-targeted 68 Ga-pentixafor PET/CT can be effectively utilized in surgical decision-making for PA patients with bilateral adrenal lesions, offering a potential alternative to AVS and may applied to predict postoperative biochemical and clinical success. Trial registration 68 Ga-Pentixafor PET/CT for Guiding Surgical Treatment of Primary Aldosteronism With Bilateral Adrenal Lesions; Trial registration number: NCT06247566; Date of registration: 2021-11-01; URL of trial registry record: https://clinicaltrials.gov/study/NCT06247566 . 68Ga-pentixafor PET/CT CXCR4 primary aldosteronism surgery decision-making bilateral adrenal lesions Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Primary aldosteronism (PA) is characterized by excessive production of renin-independent aldosterone, which increases blood volume, potassium excretion, and sodium storage in the body, accompanied by inhibition of renin-angiotensin system activity. Clinically, patients with PA often present hypertension and hypokalemia( 1 ). Furthermore, patients with PA face a significantly higher risk of cardiovascular and cerebrovascular complications compared to those with primary hypertension, even when matched for blood pressure( 2 ). PA is mainly classified into two subtypes: unilateral aldosterone hypersecretion with contralateral aldosterone non-secretion (most commonly due to unilateral aldosterone-producing adenoma [APA]) and bilateral aldosterone hypersecretion (most often resulting from idiopathic hyperaldosteronism [IHA] or bilateral APA). Accurate differentiation of these subtypes is critical, as patients with unilateral or lateralized adrenal aldosterone hypersecretion may benefit from surgical removal of the adrenal lesion. For patients without lateralization, mineralocorticoid receptor antagonists (MRAs) are the recommended treatment. PA with bilateral adrenal lesions is a more complicated situation. A small percentage of APAs that appear as bilateral nodules on CT may be misdiagnosed as IHA, while cases of IHA that appear as adrenal microadenomas on CT may be mistaken for APAs, resulting in unnecessary unilateral adrenalectomy. Adrenal vein sampling (AVS), which determines the lateralization of aldosterone hypersecretion, has long been considered the gold standard for identifying PA subtypes in patients with bilateral adrenal lesions and for guiding treatment decisions ( 3 – 5 ). However, the feasibility of AVS remains controversial because of its substantial cost, invasiveness with potential risks, and complicated technique with a relatively high failure rate ( 6 , 7 ). In regions where AVS is not feasible, patients with bilateral lesions associated with PA may be treated with MRAs as a first-line therapy. Alternatively, in certain cases, suspected aldosterone-producing lesions may be surgically resected based on imaging characteristics observed in adrenal computed tomography (CT) scans ( 8 ). In these cases, larger lesions or those exhibiting radiological features typical of cortical adenomas are typically targeted for removal. However, there is still the possibility that these lesions may be non-functional, making this empirical approach prone to treatment failure. As a result, considerable efforts have been directed towards finding a cost-effective, convenient, and non-invasive alternative to AVS. The C-X-C chemokine receptor 4 (CXCR4), a G protein-coupled transmembrane receptor, is highly expressed in aldosterone-producing tissues ( 9 ). Its expression is strongly correlated with the expression of aldosterone synthase (CYP11B2) ( 9 , 10 ). The radiolabeled ligand 68 Ga-pentixafor, which selectively binds to CXCR4 receptors on cell membranes, enables the visualization of tissues with elevated CXCR4 expression using PET/CT imaging ( 11 ). The feasibility and accuracy of 68 Ga-pentixafor PET/CT for in vivo imaging of CXCR4 receptors have been well-documented in diagnosing, staging, and evaluating treatment responses in various malignancies, including lung cancer, multiple myeloma, glioma, and sarcoma ( 12 – 15 ). Consequently, there is increasing interest in utilizing this non-invasive imaging technique for the diagnosis and subtyping PA ( 10 , 16 – 21 ). Studies have demonstrated significant differences in 68 Ga-pentixafor uptake between APA and non-functional adrenal adenomas (NFA) on PET/CT scans ( 10 , 16 , 21 ). In a previous study, it was reported 68 Ga-pentixafor PET/CT could enhance the diagnosis of PA subtypes, with the maximum standardized uptake value (SUV max ) of IHA lesions and NFAs being significantly lower than that of APAs( 21 ). APA patients with a nodule greater than 1 cm in diameter, when the maximum standard uptake value was 7.3 or greater, the specificity was 100%( 21 ). Furthermore, accumulating evidence suggests that 68 Ga-pentixafor PET/CT can facilitate non-invasive diagnosis in most PA cases, identify surgically curable PA, and demonstrate strong consistency with AVS ( 17 , 22 – 25 ). These findings indicate that 68 Ga-pentixafor PET/CT may serve as a first-line test for PA classification. However, limited research has explored the value of 68 Ga-pentixafor PET/CT in predicting surgical outcomes of PA patients, especially those with bilateral adrenal lesions. Herein, in the complicated situation of PA with bilateral adrenal lesions and the limited application of AVS, we initially employed 68 Ga-pentixafor PET/CT imaging as a non-invasive alternative to AVS, for evaluating PA patients with bilateral adrenal lesions who may benefit from surgery and monitored their prognosis to assess the clinical significance of this imaging modality in guiding surgery decision-making and treatment strategies. Methods Study population This retrospective study was approved by the Institutional Review Board of our institution (2023111517). Medical records of all patients (n = 102) diagnosed with PA and bilateral adrenal lesions at a tertiary medical center from January 1, 2020, to July 1, 2024, were reviewed. The study was registered with ClinicalTrials.gov (NCT06247566). The inclusion criteria were as follows: ( 1 ) patient has hypertension (blood pressure ≥ 140/90 mmHg or taking antihypertensive medications) and/or hypokalemia; ( 2 ) positive confirmatory test (captopril test and/or saline infusion test); ( 3 ) adrenal CT scan showing bilateral adrenal lesions. Patients with other common secondary hypertension (n = 4) and severe comorbidity potentially interfering with treatment(n = 5) were excluded. Besides, 38 patients were excluded because only CT imaging was performed, and 4 patients were excluded due to missing postoperative medical records. Ultimately, 51 patients were included in the final analysis (Fig. 1 ). Otherwise, all enrolled patients have completed a 1-mg overnight dexamethasone suppression test with negative result to exclude concurrent Cushing syndrome. Baseline information for all included patients was collected and included the following variables: age, sex, height, weight, body mass index (BMI), comorbidities, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), number of antihypertensive medications, serum potassium level, plasma aldosterone concentration (PAC), direct renin concentration (DRC), aldosterone-to-renin ratio (ARR), lesion size on CT, and pathological data. The PAC, DRC and ARR were all detected under lying condition. In addition, the max nodule diameter was utilized to present the lesion size for PA with multiple nodules. 68 Ga-pentixafor PET/CT and image analysis The 68 Ga-pentixafor was prepared as previously described( 21 ). Examinations were conducted at our institution using a specialized PET/CT scanner (Discovery 690 Elite scanner; GE Healthcare). A committee-certified nuclear medicine physician (T.T.L.), blinded to the patient's clinical records, evaluated the PET/CT data. Positive lesions were identified by visual analysis when there was a significant difference in uptake between one side of the adrenal gland and the surrounding normal adrenal tissue. Negative lesions showed similar or lower uptake compared to the surrounding adrenal tissue. The lesion's SUV max , lesion-to-liver uptake ratio (LLR), and dominant lesion-to-inferior lesion ratio (DIR) were quantified. In patients undergoing PET/CT, the dominant side of bilateral adrenal lesions was determined by an experienced radiologist through visual analysis. AVS interpretation AVS examination was performed in some confirmed PA patients with bilateral adrenal lesions. Moreover, AVS was conducted to attain a definitive diagnosis in 12 PA patients with bilateral adrenal lesions, with 5 patients successfully undergoing the procedure( 4 ). Surgical Decision-making The basis for selecting surgical lateralization is mainly determined by the multidisciplinary diagnosis and treatment (MDT) team's discussion based on the patient's examination results. Although we have repeatedly emphasized the necessity for AVS, the percentage of patients underwent for AVS remains low. The main consideration is the information from 68 Ga-pentixafor PET/CT. The patient's willingness is also taken into consideration to make the decision. When 68 Ga-pentixafor PET/CT indicated clear positive lesion and the patient was willing to proceed with surgery, we would remove the positive lesion. If bilateral adrenal lesions were positive and the patient was willing to undertake surgery, we would tent to remove the side with higher SUV max . All the patients underwent surgery had unilateral adrenalectomy. Follow-up All PA patients who consented to surgical treatment were followed up three months post-surgery in the outpatient department of our institution. The Primary Aldosteronism Surgical Outcome Study (PASO) was used to assess outcomes( 26 ). Consensus criteria were applied to evaluate the proportions of patients who achieved complete, partial, or absent clinical and biochemical success. For further analysis, we defined incomplete success as partial, or absent clinical/biochemical success in this study. Immunohistochemistry All postoperative paraffin-embedded specimens from surgical patients were subjected to immunohistochemical analysis. The antibodies used and their dilutions were as follows: CXCR4 (1:1000, 60042-1-Ig, Proteintech) and CYP11B2 (1:200 MABS1251, Millipore). Immunohistochemistry was used to assess the expression of aldosterone synthase CYP11B2 and CXCR4. The score was rated as follows: 0 points for 0%, 1 point for 0–10%, 2 points for 10–50%, 3 points for 50–75%, and 4 points for 75–100%. A score of 0–1 was considered negative, and a score of 2–4 was considered positive. All immunohistochemical results were independently evaluated by a pathologist (X.F.) who was blinded to the patient’s clinical characteristics and imaging data before the test. Statistical analysis Data analysis was performed using IBM SPSS 26.0. The Shapiro-Wilk test was conducted to test for normality of the data. Normally distributed continuous variables were analyzed using independent t-tests, whereas the Mann-Whitney test was employed to evaluate non-normally distributed variables. Count data were expressed as frequencies (%) and compared using the chi-square test or Fisher’s exact test. Data were expressed as mean ± standard deviation (χ ± S) or median (interquartile range). The receiver operating characteristic (ROC) curves were drawn to determine the predictive thresholds of the SUV max , LLR, and DIR of 68 Ga-pentixafor PET/CT in surgical outcomes. GraphPad Prism 8.0 was used for data visualization. A p value of < 0.05 was considered statistically significant. Results Patient clinical characteristics The medical records of 102 patients diagnosed with PA and bilateral adrenal lesions were reviewed. Although all patients were advised to undergo AVS, the majority declined this invasive procedure. Following the application of various exclusion criteria, a total of 55 patients (55/93, 59.14%) completed the 68 Ga-pentixafor PET/CT and 51 were deemed eligible for inclusion in the final analysis because 4 patients were excluded due to missing postoperative medical records. The performance of PET/CT is illustrated in Fig. 2 . Among the included patients, 36 (36/51, 70.59%) underwent adrenalectomy based on PET/CT results, while 15 (15/51, 29.41%) received MRAs due to non-lateralized aldosterone secretion indicated by PET/CT. The patient clinical characteristics are detailed in Table 1 . The overall cohort had a mean age of 52.63 ± 10.72 years, with 58.82% (30/51) males and 41.18% (21/51) females. No significant differences were observed between groups in age, gender distribution, or BMI. The surgical group showed higher median plasma aldosterone concentration (PAC [lying condition]: 268.0 pg/ml vs. 202.0 pg/ml) and lower serum potassium levels (median: 2.87 mmol/L vs. 3.16 mmol/L), consistent with more pronounced aldosterone hypersecretion (Table 1 ). Table 1 Demographic and clinical characteristics of study population Clinical characteristics Total n = 51 Surgical group n = 36 MRA group n = 15 p value Age (year) 52.63 ± 10.72 52.61 ± 9.65 52.67 ± 13.34 0.083 Gender Male 30 (58.82%) 19 (52.80%) 11 (73.33%) 0.517 Female 21 (41.18%) 17 (47.20%) 4 (26.67%) BMI (kg/m2) 24.86 ± 3.54 24.94 ± 3.55 24.67 ± 3.63 0.722 Duration of hypertension (year) 9.00 (2.00, 10.50) 10.00 (2.25, 10.00) 10.00 (6.00, 20.00) 0.031 Systolic pressure (mmHg) 180.0 (165.0, 200.0) 180.0 (161.3, 197.5) 180.0 (170.0, 200.0) 0.440 Diastolic pressure (mmHg) 105.0 (100.0, 110.0) 107.5 (100.0, 110.0) 105.0 (100.0, 120.0) 0.876 Mean arterial pressure (mmHg) 145.0 (135.0, 150.0) 145.0 (135.0, 150.0) 142.5 (135.0, 155.0) 0.480 Number of antihypertension medications 2.00 (1.00, 2.00) 2.00 (1.00, 2.00) 3.00 (2.00, 3.00) 0.018 Creatinine (mmol/L) 80.5 (62.7, 103.0) 84.0 (63.50, 107.43) 54.00 (37.00, 63.00) 0.787 Serum potassium (mmol/L) 3.03(2.74, 3.30) 2.87 (2.34, 3.23) 3.16 (2.80, 3.45) 1.000 PAC (lying condition) (pg/ml) 266.0 (148.0, 547.0) 268.0 (155.3, 637.8) 202.0 (115.0, 475.0) 0.235 Table 1 (continued) Demographic and clinical characteristics of study population Clinical characteristics Total n = 51 Surgical group n = 36 MRA group n = 15 p value DRC (lying condition) (uIU/ml) 1.51 (1.20, 2.17) 1.41 (0.63, 2.61) 2.17 (1.19, 2.80) 0.358 ARR (lying condition) (pg/ml/uIU/ml) 181.42 (54.0, 537.70) 220.5 (78.0, 627.2) 71.82 (47.8, 221.5) 0.136 Nodule diameter (mm) 12.0 (9.00, 17.00) 13.00 (10.25, 19.00) 11.00 (7.00, 12.000) 0.011 Opposite nodule diameter 7.00 (6.00, 10.00) 7.00 (6.00, 10.00) 7.00 (6.00, 9.00) 0.427 Ratio of nodule diameter 1.57 (1.20, 2.17) 1.73 (1.22, 2.32) 1.28 (1.17, 1.78) 0.063 Abbreviations: PET/CT, positron emission tomography/computed tomography; BMI, body mass index; PAC, plasma aldosterone concentration; DRC, direct renin concentration; ARR, aldosterone/renin ratio. Of the 36 patients who underwent functional PET/CT and surgery, the SUV max value of lesions on the surgically treated side was significantly higher than that of non-excised lesions (15.30 ± 7.18 vs. 4.91 ± 1.42, p < 0.001). As anticipated, the SUV max value of both sides of the adrenal glands in the 15 patients treated with MRAs was comparable (5.01 ± 1.45 vs. 4.63 ± 1.51, p = 0.424) (Fig. 3 ), which is more subtyping into IHA based on previous study( 21 ). Preoperative clinical features and follow-up results Preoperative and postoperative outcomes for patients who underwent adrenalectomy are detailed in Table 2 . Postoperative indicators, including blood pressure, number of antihypertensive medications, serum potassium levels, and biochemical markers, were significantly lower compared to preoperative values (Table 2 ). The complete biochemical success rate was 88.89% (32/36), and the complete clinical success rate was 77.78% (28/36) (Fig. 4 , Table 3 ). Visual analysis revealed unilateral positive lesions in 28 patients (28/36, 77.78%). All 28 patients (100%) achieved complete biochemical success, and 26 (26/28, 92.86%) achieved complete clinical success. The remaining 8 patients (8/36, 29.03%) exhibited bilateral positive lesions, with surgery performed on the side showing higher uptake. Of these, 2 patients (2/8, 25%) achieved complete clinical success, while 6 (6/8, 75%) had incomplete clinical success. Regarding biochemical outcomes, 4 patients (4/8, 50%) achieved complete success, 4 patient (4/8, 50%) experienced incomplete success (Fig. 4 ). Table 2 Preoperative and Postoperative clinical features Postoperative clinical features After Surgery Before Surgery p value Systolic pressure (mmHg) 130.0 (127.0-133.8) 180.0 (161.3, 197.5) < 0.001 Diastolic pressure (mmHg) 80.0 (74.8–88.8) 107.5 (100.0, 110.0) < 0.001 Mean arterial pressure (mmHg) 105.0 (100.0-110.0) 145.0 (135.0, 150.0) < 0.001 Number of antihypertension medications 0.00 (0.00–0.00) 2.00 (1.00, 2.00) < 0.001 Serum potassium (mmol/L) 3.90 ± 0.34 2.87 (2.34, 3.23) < 0.001 PAC (lying condition) (pg/ml) 59.5 (40.1–82.2) 268.0 (155.3, 637.8) < 0.001 DRC (lying condition) (uIU/ml) 4.23 (3.11–7.56) 1.41 (0.63, 2.61) < 0.001 ARR (lying condition) (pg/ml/uIU/ml) 11.88 (6.91–18.83) 220.5 (78.0, 627.2) < 0.001 Abbreviations: PET/CT, positron emission tomography/computed tomography; PAC, plasma aldosterone concentration; DRC, direct renin concentration; ARR, aldosterone/renin ratio. Table 3 Imaging characteristics of 68 Ga-pentixafor PET/CT in different prognosis of PA patients Total n = 36 Clinical success p value Biochemical success p value Complete Incomplete Complete Incomplete Visual analysis Unilateral positive lesions and contralateral negative lesions 28 (77.78%) 26 (72.22%) 2 (5.56%) < 0.001 28 (77.78%) 0 (0%) 0.001 Bilateral positive lesions 8 (22.22%) 2 (5.56%) 6 (16.67%) 4 (11.11%) 4 (11.11%) SUV max of the lesions 15.29 ± 7.18 17.67 ± 6.27 6.96 ± 2.01 < 0.001 15.73 ± 6.62 6.13 ± 1.80 0.012 SUV max of the opposite lesions 4.89 ± 1.42 4.85 ± 1.47 5.05 ± 1.31 0.726 5.14 ± 1.41 4.13 ± 1.10 0.291 SUV max of the liver 2.30 ± 0.55 2.27 ± 0.59 2.41 ± 0.41 0.529 2.39 ± 0.54 2.00 ± 0.61 0.562 DIR 3.35 ± 1.80 3.91 ± 1.65 1.38 ± 0.22 < 0.001 3.32 ± 1.72 1.48 ± 0.10 < 0.001 LLR 6.97 ± 3.61 8.13 ± 3.23 2.90 ± 0.67 < 0.001 6.84 ± 3.03 3.16 ± 0.76 < 0.001 Abbreviations: SUV max , the maximum standardized uptake value; DIR, dominant/inferior side uptake ratio; LLR, lesion/liver uptake ratio. Efficacy of 68 Ga-pentixafor PET/CT for predicting surgical outcomes The prognostic value of 68 Ga-pentixafor PET/CT was evaluated in the 36 surgically treated patients. Comparative analyses demonstrated that patients with complete clinical success had significantly higher SUV max values than those with incomplete success (17.67 ± 6.27 vs. 6.96 ± 2.01). Similarly, patients with complete biochemical success exhibited higher SUV max values than those with incomplete success (15.73 ± 6.62 vs. 6.13 ± 1.80). Additionally, the levels of DIR (3.91 ± 1.65 vs. 1.38 ± 0.22, p < 0.001) and LLR (8.13 ± 3.23 vs. 2.90 ± 0.67, p < 0.001) were significantly higher in the complete clinical success group compared to the incomplete success group. Similar trends were observed for biochemical success (DIR: 3.32 ± 1.72 vs. 1.48 ± 0.10, p < 0.001; LLR: 6.84 ± 3.03 vs. 3.16 ± 0.76, p < 0.001) (Table 3 ). Predictive Performance of 68 Ga-pentixafor PET/CT Indicators The sensitivity, specificity, and accuracy of 68 Ga-pentixafor PET/CT visual analysis for predicting complete clinical success were 92.86%, 75.00%, and 88.89%, respectively (Table 4 , Fig. 5 A). ROC curve analysis identified an optimal SUV max cut-off value of 10.00 for complete clinical success, with an area under the curve (AUC) of 0.9063 (95% confidence interval [CI], 0.7949–1.000, p = 0.0005). For DIR, the optimal cut-off was 1.613, with an AUC of 0.9598 (95% CI, 0.8873–1.000, p < 0.0001), sensitivity of 90.32%, specificity of 87.50%, and accuracy of 90.32%. For LLR, the optimal cut-off was 4.575, with an AUC of 0.9777 (95% CI, 0.9352–1.000, p < 0.0001), sensitivity of 85.71%, specificity of 100%, and accuracy of 88.89% (Table 4 , Fig. 5 A). Table 4 The Predictive efficacy of 68 Ga-pentixafor PET/CT based on visual and semi-quantitative analysis Sensitivity Specificity Accuracy AUC 95%CI p value Clinical success Visual analysis 92.86% 75.00% 88.89% 0.8393 0.6510-1.000 0.0038 SUV max =10.00 85.71% 87.50% 86.11% 0.9063 0.7949-1.0000 0.0005 DIR = 1.613 96.43% 87.50% 90.32% 0.9598 0.8873-1.0000 < 0.0001 LLR = 4.575 85.71% 100% 88.89% 0.9777 0.9352-1.0000 < 0.0001 Biochemical success Visual analysis 87.50% 100% 88.89% 0.9375 0.8577-1.0000 0.0048 SUV max =8.30 90.63% 100% 91.67% 0.9453 0.8705-1.0000 0.0041 DIR = 2.031 75.00% 100% 77.78% 0.8203 0.6875–0.9531 0.0390 LLR = 4.062 81.25% 100% 86.11% 0.8984 0.7921-1.0000 0.0103 Abbreviations: SUV max , the maximum standardized uptake value; DIR, dominant/inferior side uptake ratio; LLR, lesion/liver uptake ratio. When complete biochemical success was used as the endpoint, the sensitivity, specificity, and accuracy of visual analysis were 87.50%, 100%, and 88.89%, respectively (Table 4 , Fig. 5 B). The optimal SUV max cut-off for complete biochemical success was 8.30, with an AUC of 0.9453 (95% CI, 0.8577–1.000, p = 0.0048), sensitivity of 90.63%, specificity of 100%, and accuracy of 91.67%. For DIR, the optimal cut-off was 2.031, with an AUC of 0.8203 (95% CI, 0.6875–0.9531, p = 0.0390), sensitivity of 75%, specificity of 100%, and accuracy of 77.78%. For LLR, the optimal cut-off was 4.062, with an AUC of 0.8984 (95% CI, 0.7921–1.000, p = 0.0103), sensitivity of 81.25%, specificity of 100%, and accuracy of 86.11% (Table 4 , Fig. 5 B). Postoperative pathological results Postoperative pathological results were analyzed to explore factors contributing to better surgical outcomes in patients undergoing 68 Ga-pentixafor PET/CT. All these patients exhibited prominently positive CXCR4 staining. Among the 36 patients, 77.78% (28/36) were diagnosed with adrenocortical adenoma, showing positive CYP11B2 expression (Fig. 6 A). Additionally, 8.33% (3/36) had adrenocortical adenomas without CYP11B2 expression but with significant CXCR4 expression (Fig. 6 B). Conversely, 13.89% (5/36) were diagnosed with adrenocortical hyperplasia, with 3 showing positive CYP11B2 expression and 2 showing negative staining. All hyperplastic lesions exhibited mild CXCR4 expression (Fig. 6 C-D). Overall, the consistency between CXCR4 and CYP11B2 expression was 86.11% (31/36). Comparison between AVS and 68 Ga-pentixafor PET/CT In our cohort, 5 patients underwent both successful AVS and 68 Ga-pentixafor PET/CT. The consistency between the two methods was 80% (4/5). Two patients showed concordant lateralization on both tests and achieved complete clinical and biochemical success, with pathological findings confirming CYP11B2-positive cortical adenomas. However, one patient exhibited unilateral lateralization on PET/CT but no dominant secretion on AVS; unilateral adrenalectomy resulted in clinical and biochemical success, with pathological confirmation of a CYP11B2-positive cortical adenoma. The remaining two patients showed no lateralization on either AVS or 68 Ga-pentixafor PET/CT test, resulting in medical treatment (Table 5 ). Table 5 Comparison of AVS and 68 Ga-pentixafor PET/CT Imaging Results Patient AVS 68 Ga-pentixafor PET/CT Pathological result CYP11B2 Biochemical success Clinical success Lateralization LI Lateralization SUV max LLR DIR 1 L 13.79 L 14.9 8.28 5.14 Adenoma Positive Complete Complete 2 L 2.78 L 14.8 7.40 3.36 Adenoma Positive Complete Complete 3 B 1.35 R 15.8 6.58 2.26 Adenoma Positive Complete Complete 4 B 1.75 B 5.3 2.21 1.33 Medical treatment 5 B 1.41 B 4.3 2.35 1.02 Medical treatment Abbreviations: AVS, adrenal vein sampling; LI, lateralization index; L, left; B, bilateral; R, right. Discussion This retrospective analysis demonstrates that surgical intervention guided by CXCR4-targeted 68 Ga-pentixafor PET/CT achieves favorable clinical and biochemical outcomes in PA patients with bilateral adrenal lesions. Parameters including visual analysis, SUV max , LLR, and DIR effectively identified surgical candidates, suggesting CXCR4-based functional imaging could circumvent the need for AVS in this complex subgroup. Precision and noninvasiveness diagnostics of disease is currently an emerging trend in the clinic. Our study proposes a paradigm shift toward CXCR4 PET/CT-guided surgery decision-making in AVS-free way for PA patients with bilateral adrenal lesions. Current guidelines recommend using AVS as the gold standard for PA lateralization and treatment selection ( 4 , 27 – 29 ). However, technical limitations, inconsistent use criteria, and high failure rates hinder widespread adoption of AVS ( 30 , 31 ). Despite the introduction of AVS at our center in 2020, only 12 out of 51 (23.53%) PA patients with bilateral adrenal lesions successfully underwent AVS in this study. Notably, the 80% concordance between 68 Ga-pentixafor PET/CT and AVS lateralization in our study, coupled with superior surgical outcome prediction (100% vs. 67%), indicated the potential to replace AVS. Our results echo the reports from other investigators, in which the tests showed a 66.7% − 90% concordance rate and 68 Ga-pentixafor PET/CT was equal to or even better than AVS in predicting outcomes after surgery( 17 – 19 , 23 , 25 ). Previous studies predominantly focused on unilateral PA patients, with only a small subset of patients with bilateral lesions included. Discrepancies among these studies could be attributed to variations in sample size and characteristics. Before considering revisions to the guidelines, further investigation is warranted to determine whether 68 Ga-pentixafor PET/CT can serve as a cost-effective, convenient, and non-invasive alternative to AVS. Multiple studies have demonstrated the reliability of CXCR4-targeted functional imaging in identifying aldosterone-secreting nodules and classifying PA ( 9 , 10 , 16 – 19 , 21 , 32 ). For instance, Ding et al. reported that the SUVmax value of APAs (15.3 ± 7.7) was significantly higher than that of suspected unilateral adrenal hyperplasia (UAH) (9.1 ± 2.7), IHA (4.3 ± 1.3), and NFA (4.4 ± 1.7) ( 18 ). Similarly, a previous study found a median SUV max value of 14.5 in APAs, which was notably higher than that of IHA (4.8) and NFA (4.65) ( 21 ). In our study, the average SUV max value of adrenal lesions selected for surgical removal was 15.30 ± 7.18, underscoring the significant utility of 68 Ga-pentixafor PET/CT in guiding surgical decision-making for bilateral adrenal lesions by effectively identifying aldosterone-producing nodules such as APAs. This finding was further corroborated by postoperative pathological analysis. Notably, 68 Ga-pentixafor PET/CT demonstrated superior performance in identifying APAs with positive CYP11B2 expression (77.8%, 28/36). Our results support the high concordance rate between CXCR4 and CYP11B2 expression, as previously reported( 10 , 16 , 21 , 32 ). However, two patients with CYP11B2-negative/CXCR4-positive adenomas still achieved biochemical remission, suggesting alternative aldosterone-secreting mechanisms linked to somatic mutations( 32 – 35 ), which this phenomenon warranted investigation into whether CXCR4 overexpression reflects latent autonomous secretion despite negative CYP11B2 staining. Evidence from various studies has demonstrated the utility of several indicators of CXCR4-targeted 68 Ga-pentixafor PET/CT imaging—such as visualization, LLR, and lesion-to-contralateral adrenal gland ratio (LCR)—in distinguishing and predicting APAs ( 10 , 16 – 19 , 21 , 32 ). However, most of these studies prioritized pathological diagnosis and provided limited insights into prognosis. Recently, Ding et al. reported that 68 Ga-pentixafor PET/CT could differentiate surgically eligible from ineligible micronodules, primarily based on surgical pathology and outcomes ( 19 ). Notably, all adrenal lesions analyzed in their study were smaller than 1 cm, with the majority being unilateral. To our knowledge, this is the first study to evaluate the efficacy of 68 Ga-pentixafor PET/CT in predicting surgical outcomes for PA patients with bilateral adrenal lesions, a scenario that poses greater complexity and challenges in clinical practice. Our findings suggest that visual assessment of 68 Ga-pentixafor PET/CT images and semiquantitative analysis of PET data may be sufficient to predict adrenalectomy outcomes in PA patients with bilateral adrenal lesions with high accuracy. Specifically, patients diagnosed with lateralized disease, characterized by unilateral positive or asymmetrically bilateral positive lesions, may benefit from the removal of the affected adrenal gland. Interestingly, unlike previous studies focused on identifying APAs, the application of semiquantitative analysis of 68 Ga-pentixafor PET data to predict surgical outcomes may require a relatively higher SUV max cut-off value. This discrepancy may be partially attributed to the complexity of predicting PA prognosis. In fact, surgical outcomes in PA patients are influenced not only by pathological classification but also by confounding factors such as primary hypertension and comorbidities like chronic renal failure, which warrant further investigation ( 8 , 36 ). This study has several limitations. First, its retrospective nature and single-center design may have introduced selection bias and influenced the findings. Second, the limited sample size, resulting from our focus on bilateral adrenal lesions, might have led to insufficient statistical significance and biased outcomes. Third, although high-resolution adrenal CT was used to initially detect bilateral adrenal lesions, some microadenomas or smaller lesions might have been missed. Additionally, most tumor lesions in our study were ≥ 1 cm in diameter, which hindered the analysis of the diagnostic efficacy of PET/CT for nodules smaller than 1 cm, potentially introducing uncertainty into our results. Importantly, since most patients declined the AVS test, we could not assess the potential of false negative results of 68 Ga-pentixafor PET/CT, which may influence treatment decisions. Furthermore, the majority of treatment decisions in this study were based on 68 Ga-pentixafor PET/CT without AVS, which may represent another potential source of bias. Therefore, we emphasize the need for a large-scale, prospective, randomized, controlled, multicenter trial to further validate the applicability of 68 Ga-pentixafor PET/CT as an alternative to AVS in guiding surgical treatment for PA patients. Conclusion In summary, this retrospective study demonstrates that CXCR4-targeted 68 Ga-pentixafor PET/CT can be effectively utilized for surgical decision-making in PA patients with bilateral adrenal lesions, providing a potential alternative to AVS for prognostic prediction. This study lays a solid foundation for future randomized controlled trials comparing 68 Ga-pentixafor PET/CT with AVS in patients with PA and bilateral adrenal lesions. Declarations Acknowledgments: We thank the MJ Language Editing Services (https://www.mjeditor.com) for its linguistic assistance during the preparation of this manuscript. Author contributions: All authors contributed to the study conception and design and commented on previous versions of the manuscript. All authors read and approved the final manuscript. The contributions of every author are as follows: conceptualization: Yu Gan, Longfei Liu, Kai Cheng; data curation: Zhiwei Shu, Yao He, Min Guo, Zhuying Xia, Xiaodan Fu, Bingsheng Li, Bo Zhang, Yi Yang, Jiaxian Chen; PET imaging acquisition: Tingting Long; formal analysis: Zhiwei Shu, Yao He; Writing-original draft: Zhiwei Shu, Yao He; Writing-review & editing: Tiejian Jiang, Xiang Chen, Yu Gan, Longfei Liu, Kai Cheng; funding acquisition: Yu Gan, Longfei Liu. Funding: This study was funded by National Natural Science Foundation of China (82273121), Hunan Natural Science Foundation (2022JJ20096), and National Research Center for Clinical Medicine of Geriatric Diseases Clinical Research Fund (2022LNJJ12). Data availability: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate: This study was approved by the ethics committee of the Xiangya Hospital, Central South University (2023111517). This article does not contain any experiments with animals. Informed consent was obtained from all individual participants included in the study. Consent for publication: Written informed consent was obtained from the patient for publication of this study and accompanying images. Consent to participate: Competing interests: The authors have no competing interests to disclose in relation with this article References Choy KW, Fuller PJ, Russell G, Li Q, Leenaerts M, Yang J. Primary aldosteronism. BMJ (Clinical Res ed). 2022;377:e065250. Monticone S, D'Ascenzo F, Moretti C, Williams TA, Veglio F, Gaita F, et al. Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta-analysis. lancet Diabetes Endocrinol. 2018;6(1):41–50. 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Roles of clinical criteria, computed tomography scan, and adrenal vein sampling in differential diagnosis of primary aldosteronism subtypes. J Clin Endocrinol Metab. 2008;93(4):1366–71. Lim V, Guo Q, Grant CS, Thompson GB, Richards ML, Farley DR, et al. Accuracy of adrenal imaging and adrenal venous sampling in predicting surgical cure of primary aldosteronism. J Clin Endocrinol Metab. 2014;99(8):2712–9. Dekkers T, Prejbisz A, Kool LJS, Groenewoud H, Velema M, Spiering W, et al. Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcome-based randomised diagnostic trial. lancet Diabetes Endocrinol. 2016;4(9):739–46. Lee SE, Park SW, Choi MS, Kim G, Yoo JH, Ahn J, et al. Primary aldosteronism subtyping in the setting of partially successful adrenal vein sampling. Therapeutic Adv Endocrinol metabolism. 2021;12:2042018821989239. Zheng Y, Long T, Peng N, Zhen M, Ye Q, Zhang Z et al. The Value of Targeting CXCR4 with 68Ga-Pentixafor PET/CT for Subtyping Primary Aldosteronism. J Clin Endocrinol Metab. 2023. De Sousa K, Boulkroun S, Baron S, Nanba K, Wack M, Rainey WE, Genetic, Cellular, and Molecular Heterogeneity in Adrenals With Aldosterone-Producing Adenoma., Hypertension et al. Dallas, Tex: (1979). 2020;75(4):1034-44. Monticone S, Castellano I, Versace K, Lucatello B, Veglio F, Gomez-Sanchez CE, et al. Immunohistochemical, genetic and clinical characterization of sporadic aldosterone-producing adenomas. Mol Cell Endocrinol. 2015;411:146–54. Dekkers T, ter Meer M, Lenders JW, Hermus AR, Schultze Kool L, Langenhuijsen JF, et al. Adrenal nodularity and somatic mutations in primary aldosteronism: one node is the culprit? J Clin Endocrinol Metab. 2014;99(7):E1341–51. Burrello J, Burrello A, Stowasser M, Nishikawa T, Quinkler M, Prejbisz A, et al. The Primary Aldosteronism Surgical Outcome Score for the Prediction of Clinical Outcomes After Adrenalectomy for Unilateral Primary Aldosteronism. Ann Surg. 2020;272(6):1125–32. Cite Share Download PDF Status: Published Journal Publication published 28 Aug, 2025 Read the published version in EJNMMI Research → Version 1 posted Reviewers agreed at journal 11 May, 2025 Reviewers invited by journal 25 Apr, 2025 Editor assigned by journal 11 Apr, 2025 First submitted to journal 11 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6385295","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":447918222,"identity":"03cb88c1-183f-4e7b-ac59-244a1f1234ac","order_by":0,"name":"Zhiwei Shu","email":"","orcid":"","institution":"Xiangya Hospital Central South University","correspondingAuthor":false,"prefix":"","firstName":"Zhiwei","middleName":"","lastName":"Shu","suffix":""},{"id":447918223,"identity":"36da8f08-a8d2-4585-826e-aac9fc472f34","order_by":1,"name":"Yao He","email":"","orcid":"","institution":"Xiangya Hospital Central South 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07:25:49","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6385295/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6385295/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13550-025-01309-4","type":"published","date":"2025-08-28T15:57:57+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82280681,"identity":"7008cb9b-2ec7-4056-b7aa-c7b333d1ae14","added_by":"auto","created_at":"2025-05-08 15:12:20","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":262325,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlow chart of patient cohort selection. \u003c/strong\u003ePET/CT, positron emission tomography/computer tomography; CT, computed tomography; MRAs, mineralocorticoid-receptor antagonists.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-6385295/v1/468db9aa4412f71a3f2f069b.png"},{"id":82278448,"identity":"4b9d9f9d-26af-4acc-8324-b4aec29b0790","added_by":"auto","created_at":"2025-05-08 14:56:20","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":459082,"visible":true,"origin":"","legend":"\u003cp\u003e\u003csup\u003e\u003cstrong\u003e68\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003eGa-pentixafor PET/CT imaging findings in PA patients with bilateral adrenal lesions.\u003c/strong\u003e \u003cstrong\u003eA.\u003c/strong\u003e \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT images demonstrating positive lesions on one side and negative lesions on the other. A 52-year-old man, presented with persistent hypertension and hypokalemia for 10 years. ARR exceeding 30, peak blood pressure of 180/110 mmHg and minimum blood potassium level of 2.93mmol/l. CT scans revealed bilateral lesions in the adrenal glands (indicated by arrows, the white arrows mean negative lesions, and yellow arrows mean positive), with PET/CT showing a notably higher SUV\u003csub\u003emax\u003c/sub\u003e in the left adrenal gland lesion (SUV\u003csub\u003emax\u003c/sub\u003e = 26.8, yellow arrows) compared to the right (SUV\u003csub\u003emax\u003c/sub\u003e = 4.6, white arrows). \u003cstrong\u003eB.\u003c/strong\u003e Images showing positive lesions on both sides in a 53-year-old-man with 20 years hypertension and hypokalemia, ARR \u0026gt;30, maximum blood pressure of 210/110 mmHg, and minimum blood potassium of 1.98 mmol/l, CT showed bilateral adrenal lesions (yellow arrows), and PET/CT exhibited positive lesions on both side (SUV\u003csub\u003emax\u003c/sub\u003e = 9.8 vs.7.2, yellow arrows). \u003cstrong\u003eC. \u003c/strong\u003eImages displaying negative lesions on both sides in a 69-year-old-woman with 30 years of hypertension and hypokalemia. ARR \u0026gt;30, maximum blood pressure of 190/120 mmHg, and minimum blood potassium of 3.28 mmol/l. CT showed bilateral adrenal lesions (white arrows), and PET/CT exhibited similar values of bilateral adrenal uptake (SUV\u003csub\u003emax\u003c/sub\u003e = 3.4 vs. 3.5, white arrows). PA, primary aldosteronism; ARR, aldosterone-to-renin ratio; SUV\u003csub\u003emax\u003c/sub\u003e, the maximum standardized uptake value.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-6385295/v1/1c0f9d79c6cbe9d8abf6c285.png"},{"id":82278440,"identity":"c2644cd8-4f43-4387-9b43-8e7956db411d","added_by":"auto","created_at":"2025-05-08 14:56:20","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":142305,"visible":true,"origin":"","legend":"\u003cp\u003e\u003csup\u003e\u003cstrong\u003e68\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003eGa-pentixafor PET/CT imaging findings in PA patients with bilateral adrenal lesions.\u003c/strong\u003e ***\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-6385295/v1/4846496ceb4892d99ac9c22d.png"},{"id":82279374,"identity":"f5eb7312-7cf7-4a48-9fc1-46f46132dbf5","added_by":"auto","created_at":"2025-05-08 15:04:20","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":256672,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRate of biochemical and clinical success of patients underwent surgery.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-6385295/v1/7bc7950450e9e1bc006f1907.png"},{"id":82279372,"identity":"5c8ffbc1-d141-4e02-9106-40e32305918d","added_by":"auto","created_at":"2025-05-08 15:04:20","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":337481,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe ROC curve of SUV\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003emax\u003c/strong\u003e\u003c/sub\u003e\u003cstrong\u003e, DIR, and LLR for predicting outcomes. A.\u003c/strong\u003e The ROC curve of SUV\u003csub\u003emax\u003c/sub\u003e, DIR, and LLR for predicting clinical success; \u003cstrong\u003eB.\u003c/strong\u003e The ROC curve of SUV\u003csub\u003emax\u003c/sub\u003e, DIR, and LLR for predicting biochemical success. Receiver-operating characteristic; AUC, area under the ROC curve; LLR, lesion/liver uptake ratio; DIR, dominant/inferior side uptake ratio.\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-6385295/v1/a3189fa40982f056d0bb969e.png"},{"id":82278454,"identity":"d8af0e4a-2e96-467f-8897-ca3c19183653","added_by":"auto","created_at":"2025-05-08 14:56:20","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":1179353,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePathological subtypes of PA patients and their postoperative immunohistochemical results.\u003c/strong\u003e \u003cstrong\u003eA.\u003c/strong\u003e Adrenal cortical adenoma with positive CYP11B2 and positive CXCR4 expression; \u003cstrong\u003eB.\u003c/strong\u003e Adrenal cortical adenoma with negative CYP11B2 expression and positive CXCR4 expression; \u003cstrong\u003eC.\u003c/strong\u003e Adrenal cortical adenoma-like hyperplasia with positive CYP11B2 and positive CXCR4 expression; \u003cstrong\u003eD.\u003c/strong\u003e Adrenal cortical adenoma-like hyperplasia with negative CYP11B2 and positive CXCR4 expression. (magnification 100×, bar = 100μm)\u003c/p\u003e","description":"","filename":"Figure6.png","url":"https://assets-eu.researchsquare.com/files/rs-6385295/v1/19be64febf2d1270b662c8bc.png"},{"id":90345598,"identity":"eb479b25-12bf-42f4-90a9-53cbefd30761","added_by":"auto","created_at":"2025-09-01 16:10:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4044531,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6385295/v1/236379da-42da-4a71-b79e-55ae52a72bb0.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eIs CXCR4-Targeted \u003csup\u003e68\u003c/sup\u003eGa-Pentixafor PET/CT a Reliable AVS-free Modality for Surgical Decision-making and Prognostic Prediction in Primary Aldosteronism with Bilateral Adrenal Lesions?\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePrimary aldosteronism (PA) is characterized by excessive production of renin-independent aldosterone, which increases blood volume, potassium excretion, and sodium storage in the body, accompanied by inhibition of renin-angiotensin system activity. Clinically, patients with PA often present hypertension and hypokalemia(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Furthermore, patients with PA face a significantly higher risk of cardiovascular and cerebrovascular complications compared to those with primary hypertension, even when matched for blood pressure(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). PA is mainly classified into two subtypes: unilateral aldosterone hypersecretion with contralateral aldosterone non-secretion (most commonly due to unilateral aldosterone-producing adenoma [APA]) and bilateral aldosterone hypersecretion (most often resulting from idiopathic hyperaldosteronism [IHA] or bilateral APA). Accurate differentiation of these subtypes is critical, as patients with unilateral or lateralized adrenal aldosterone hypersecretion may benefit from surgical removal of the adrenal lesion. For patients without lateralization, mineralocorticoid receptor antagonists (MRAs) are the recommended treatment. PA with bilateral adrenal lesions is a more complicated situation. A small percentage of APAs that appear as bilateral nodules on CT may be misdiagnosed as IHA, while cases of IHA that appear as adrenal microadenomas on CT may be mistaken for APAs, resulting in unnecessary unilateral adrenalectomy.\u003c/p\u003e \u003cp\u003eAdrenal vein sampling (AVS), which determines the lateralization of aldosterone hypersecretion, has long been considered the gold standard for identifying PA subtypes in patients with bilateral adrenal lesions and for guiding treatment decisions (\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). However, the feasibility of AVS remains controversial because of its substantial cost, invasiveness with potential risks, and complicated technique with a relatively high failure rate (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). In regions where AVS is not feasible, patients with bilateral lesions associated with PA may be treated with MRAs as a first-line therapy. Alternatively, in certain cases, suspected aldosterone-producing lesions may be surgically resected based on imaging characteristics observed in adrenal computed tomography (CT) scans (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). In these cases, larger lesions or those exhibiting radiological features typical of cortical adenomas are typically targeted for removal. However, there is still the possibility that these lesions may be non-functional, making this empirical approach prone to treatment failure. As a result, considerable efforts have been directed towards finding a cost-effective, convenient, and non-invasive alternative to AVS.\u003c/p\u003e \u003cp\u003eThe C-X-C chemokine receptor 4 (CXCR4), a G protein-coupled transmembrane receptor, is highly expressed in aldosterone-producing tissues (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Its expression is strongly correlated with the expression of aldosterone synthase (CYP11B2) (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). The radiolabeled ligand \u003csup\u003e68\u003c/sup\u003eGa-pentixafor, which selectively binds to CXCR4 receptors on cell membranes, enables the visualization of tissues with elevated CXCR4 expression using PET/CT imaging (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). The feasibility and accuracy of \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT for in vivo imaging of CXCR4 receptors have been well-documented in diagnosing, staging, and evaluating treatment responses in various malignancies, including lung cancer, multiple myeloma, glioma, and sarcoma (\u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Consequently, there is increasing interest in utilizing this non-invasive imaging technique for the diagnosis and subtyping PA (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan additionalcitationids=\"CR17 CR18 CR19 CR20\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eStudies have demonstrated significant differences in \u003csup\u003e68\u003c/sup\u003eGa-pentixafor uptake between APA and non-functional adrenal adenomas (NFA) on PET/CT scans (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). In a previous study, it was reported \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT could enhance the diagnosis of PA subtypes, with the maximum standardized uptake value (SUV\u003csub\u003emax\u003c/sub\u003e) of IHA lesions and NFAs being significantly lower than that of APAs(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). APA patients with a nodule greater than 1 cm in diameter, when the maximum standard uptake value was 7.3 or greater, the specificity was 100%(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Furthermore, accumulating evidence suggests that \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT can facilitate non-invasive diagnosis in most PA cases, identify surgically curable PA, and demonstrate strong consistency with AVS (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan additionalcitationids=\"CR23 CR24\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). These findings indicate that \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT may serve as a first-line test for PA classification. However, limited research has explored the value of \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT in predicting surgical outcomes of PA patients, especially those with bilateral adrenal lesions. Herein, in the complicated situation of PA with bilateral adrenal lesions and the limited application of AVS, we initially employed \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT imaging as a non-invasive alternative to AVS, for evaluating PA patients with bilateral adrenal lesions who may benefit from surgery and monitored their prognosis to assess the clinical significance of this imaging modality in guiding surgery decision-making and treatment strategies.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003e This retrospective study was approved by the Institutional Review Board of our institution (2023111517). Medical records of all patients (n\u0026thinsp;=\u0026thinsp;102) diagnosed with PA and bilateral adrenal lesions at a tertiary medical center from January 1, 2020, to July 1, 2024, were reviewed. The study was registered with ClinicalTrials.gov (NCT06247566). The inclusion criteria were as follows: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) patient has hypertension (blood pressure\u0026thinsp;\u0026ge;\u0026thinsp;140/90 mmHg or taking antihypertensive medications) and/or hypokalemia; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) positive confirmatory test (captopril test and/or saline infusion test); (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) adrenal CT scan showing bilateral adrenal lesions. Patients with other common secondary hypertension (n\u0026thinsp;=\u0026thinsp;4) and severe comorbidity potentially interfering with treatment(n\u0026thinsp;=\u0026thinsp;5) were excluded. Besides, 38 patients were excluded because only CT imaging was performed, and 4 patients were excluded due to missing postoperative medical records. Ultimately, 51 patients were included in the final analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Otherwise, all enrolled patients have completed a 1-mg overnight dexamethasone suppression test with negative result to exclude concurrent Cushing syndrome.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBaseline information for all included patients was collected and included the following variables: age, sex, height, weight, body mass index (BMI), comorbidities, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), number of antihypertensive medications, serum potassium level, plasma aldosterone concentration (PAC), direct renin concentration (DRC), aldosterone-to-renin ratio (ARR), lesion size on CT, and pathological data. The PAC, DRC and ARR were all detected under lying condition. In addition, the max nodule diameter was utilized to present the lesion size for PA with multiple nodules.\u003c/p\u003e \u003cp\u003e \u003csup\u003e \u003cb\u003e68\u003c/b\u003e \u003c/sup\u003e \u003cb\u003eGa-pentixafor PET/CT and image analysis\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe \u003csup\u003e68\u003c/sup\u003eGa-pentixafor was prepared as previously described(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Examinations were conducted at our institution using a specialized PET/CT scanner (Discovery 690 Elite scanner; GE Healthcare). A committee-certified nuclear medicine physician (T.T.L.), blinded to the patient's clinical records, evaluated the PET/CT data. Positive lesions were identified by visual analysis when there was a significant difference in uptake between one side of the adrenal gland and the surrounding normal adrenal tissue. Negative lesions showed similar or lower uptake compared to the surrounding adrenal tissue. The lesion's SUV\u003csub\u003emax\u003c/sub\u003e, lesion-to-liver uptake ratio (LLR), and dominant lesion-to-inferior lesion ratio (DIR) were quantified. In patients undergoing PET/CT, the dominant side of bilateral adrenal lesions was determined by an experienced radiologist through visual analysis.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAVS interpretation\u003c/h3\u003e\n\u003cp\u003eAVS examination was performed in some confirmed PA patients with bilateral adrenal lesions. Moreover, AVS was conducted to attain a definitive diagnosis in 12 PA patients with bilateral adrenal lesions, with 5 patients successfully undergoing the procedure(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eSurgical Decision-making\u003c/h3\u003e\n\u003cp\u003eThe basis for selecting surgical lateralization is mainly determined by the multidisciplinary diagnosis and treatment (MDT) team's discussion based on the patient's examination results. Although we have repeatedly emphasized the necessity for AVS, the percentage of patients underwent for AVS remains low. The main consideration is the information from \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT. The patient's willingness is also taken into consideration to make the decision. When \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT indicated clear positive lesion and the patient was willing to proceed with surgery, we would remove the positive lesion. If bilateral adrenal lesions were positive and the patient was willing to undertake surgery, we would tent to remove the side with higher SUV\u003csub\u003emax\u003c/sub\u003e. All the patients underwent surgery had unilateral adrenalectomy.\u003c/p\u003e\n\u003ch3\u003eFollow-up\u003c/h3\u003e\n\u003cp\u003eAll PA patients who consented to surgical treatment were followed up three months post-surgery in the outpatient department of our institution. The Primary Aldosteronism Surgical Outcome Study (PASO) was used to assess outcomes(\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Consensus criteria were applied to evaluate the proportions of patients who achieved complete, partial, or absent clinical and biochemical success. For further analysis, we defined incomplete success as partial, or absent clinical/biochemical success in this study.\u003c/p\u003e\n\u003ch3\u003eImmunohistochemistry\u003c/h3\u003e\n\u003cp\u003eAll postoperative paraffin-embedded specimens from surgical patients were subjected to immunohistochemical analysis. The antibodies used and their dilutions were as follows: CXCR4 (1:1000, 60042-1-Ig, Proteintech) and CYP11B2 (1:200 MABS1251, Millipore). Immunohistochemistry was used to assess the expression of aldosterone synthase CYP11B2 and CXCR4. The score was rated as follows: 0 points for 0%, 1 point for 0\u0026ndash;10%, 2 points for 10\u0026ndash;50%, 3 points for 50\u0026ndash;75%, and 4 points for 75\u0026ndash;100%. A score of 0\u0026ndash;1 was considered negative, and a score of 2\u0026ndash;4 was considered positive. All immunohistochemical results were independently evaluated by a pathologist (X.F.) who was blinded to the patient\u0026rsquo;s clinical characteristics and imaging data before the test.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData analysis was performed using IBM SPSS 26.0. The Shapiro-Wilk test was conducted to test for normality of the data. Normally distributed continuous variables were analyzed using independent t-tests, whereas the Mann-Whitney test was employed to evaluate non-normally distributed variables. Count data were expressed as frequencies (%) and compared using the chi-square test or Fisher\u0026rsquo;s exact test. Data were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (χ\u0026thinsp;\u0026plusmn;\u0026thinsp;S) or median (interquartile range). The receiver operating characteristic (ROC) curves were drawn to determine the predictive thresholds of the SUV\u003csub\u003emax\u003c/sub\u003e, LLR, and DIR of \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT in surgical outcomes. GraphPad Prism 8.0 was used for data visualization. A \u003cem\u003ep\u003c/em\u003e value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003ePatient clinical characteristics\u003c/h2\u003e \u003cp\u003eThe medical records of 102 patients diagnosed with PA and bilateral adrenal lesions were reviewed. Although all patients were advised to undergo AVS, the majority declined this invasive procedure. Following the application of various exclusion criteria, a total of 55 patients (55/93, 59.14%) completed the \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT and 51 were deemed eligible for inclusion in the final analysis because 4 patients were excluded due to missing postoperative medical records. The performance of PET/CT is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Among the included patients, 36 (36/51, 70.59%) underwent adrenalectomy based on PET/CT results, while 15 (15/51, 29.41%) received MRAs due to non-lateralized aldosterone secretion indicated by PET/CT. The patient clinical characteristics are detailed in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The overall cohort had a mean age of 52.63\u0026thinsp;\u0026plusmn;\u0026thinsp;10.72 years, with 58.82% (30/51) males and 41.18% (21/51) females. No significant differences were observed between groups in age, gender distribution, or BMI. The surgical group showed higher median plasma aldosterone concentration (PAC [lying condition]: 268.0 pg/ml vs. 202.0 pg/ml) and lower serum potassium levels (median: 2.87 mmol/L vs. 3.16 mmol/L), consistent with more pronounced aldosterone hypersecretion (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic and clinical characteristics of study population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;51\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSurgical group\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;36\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMRA group\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;15\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52.63\u0026thinsp;\u0026plusmn;\u0026thinsp;10.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52.61\u0026thinsp;\u0026plusmn;\u0026thinsp;9.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e52.67\u0026thinsp;\u0026plusmn;\u0026thinsp;13.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.083\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (58.82%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (52.80%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (73.33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.517\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (41.18%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (47.20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (26.67%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.86\u0026thinsp;\u0026plusmn;\u0026thinsp;3.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.94\u0026thinsp;\u0026plusmn;\u0026thinsp;3.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.67\u0026thinsp;\u0026plusmn;\u0026thinsp;3.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.722\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of hypertension (year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.00 (2.00, 10.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.00 (2.25, 10.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.00 (6.00, 20.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.031\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSystolic pressure (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e180.0 (165.0, 200.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e180.0 (161.3, 197.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e180.0 (170.0, 200.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.440\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiastolic pressure (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e105.0 (100.0, 110.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e107.5 (100.0, 110.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e105.0 (100.0, 120.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.876\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean arterial pressure (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e145.0 (135.0, 150.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e145.0 (135.0, 150.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e142.5 (135.0, 155.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.480\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of antihypertension medications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.00 (1.00, 2.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.00 (1.00, 2.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.00 (2.00, 3.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.018\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80.5 (62.7, 103.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84.0 (63.50, 107.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e54.00 (37.00, 63.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.787\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum potassium (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.03(2.74, 3.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.87 (2.34, 3.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.16 (2.80, 3.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePAC (lying condition) (pg/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e266.0 (148.0, 547.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e268.0 (155.3, 637.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e202.0 (115.0, 475.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.235\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e(continued) Demographic and clinical characteristics of study population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;51\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSurgical group\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;36\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMRA group\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;15\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDRC (lying condition) (uIU/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.51 (1.20, 2.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.41 (0.63, 2.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.17 (1.19, 2.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.358\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eARR (lying condition) (pg/ml/uIU/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e181.42 (54.0, 537.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e220.5 (78.0, 627.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e71.82 (47.8, 221.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.136\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNodule diameter (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.0 (9.00, 17.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.00 (10.25, 19.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.00 (7.00, 12.000)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOpposite nodule diameter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.00 (6.00, 10.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.00 (6.00, 10.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.00 (6.00, 9.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.427\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRatio of nodule diameter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.57 (1.20, 2.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.73 (1.22, 2.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.28 (1.17, 1.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.063\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e PET/CT, positron emission tomography/computed tomography; BMI, body mass index; PAC, plasma aldosterone concentration; DRC, direct renin concentration; ARR, aldosterone/renin ratio.\u003c/p\u003e\u003cp\u003eOf the 36 patients who underwent functional PET/CT and surgery, the SUV\u003csub\u003emax\u003c/sub\u003e value of lesions on the surgically treated side was significantly higher than that of non-excised lesions (15.30\u0026thinsp;\u0026plusmn;\u0026thinsp;7.18 vs. 4.91\u0026thinsp;\u0026plusmn;\u0026thinsp;1.42, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). As anticipated, the SUV\u003csub\u003emax\u003c/sub\u003e value of both sides of the adrenal glands in the 15 patients treated with MRAs was comparable (5.01\u0026thinsp;\u0026plusmn;\u0026thinsp;1.45 vs. 4.63\u0026thinsp;\u0026plusmn;\u0026thinsp;1.51, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.424) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), which is more subtyping into IHA based on previous study(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePreoperative clinical features and follow-up results\u003c/h2\u003e \u003cp\u003ePreoperative and postoperative outcomes for patients who underwent adrenalectomy are detailed in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Postoperative indicators, including blood pressure, number of antihypertensive medications, serum potassium levels, and biochemical markers, were significantly lower compared to preoperative values (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The complete biochemical success rate was 88.89% (32/36), and the complete clinical success rate was 77.78% (28/36) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Visual analysis revealed unilateral positive lesions in 28 patients (28/36, 77.78%). All 28 patients (100%) achieved complete biochemical success, and 26 (26/28, 92.86%) achieved complete clinical success. The remaining 8 patients (8/36, 29.03%) exhibited bilateral positive lesions, with surgery performed on the side showing higher uptake. Of these, 2 patients (2/8, 25%) achieved complete clinical success, while 6 (6/8, 75%) had incomplete clinical success. Regarding biochemical outcomes, 4 patients (4/8, 50%) achieved complete success, 4 patient (4/8, 50%) experienced incomplete success (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePreoperative and Postoperative clinical features\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative clinical features\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAfter Surgery\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBefore Surgery\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSystolic pressure (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e130.0 (127.0-133.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e180.0 (161.3, 197.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiastolic pressure (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80.0 (74.8\u0026ndash;88.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e107.5 (100.0, 110.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean arterial pressure (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e105.0 (100.0-110.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e145.0 (135.0, 150.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of antihypertension medications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00 (0.00\u0026ndash;0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.00 (1.00, 2.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum potassium (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.90\u0026thinsp;\u0026plusmn;\u0026thinsp;0.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.87 (2.34, 3.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePAC (lying condition) (pg/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59.5 (40.1\u0026ndash;82.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e268.0 (155.3, 637.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDRC (lying condition) (uIU/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.23 (3.11\u0026ndash;7.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.41 (0.63, 2.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eARR (lying condition) (pg/ml/uIU/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.88 (6.91\u0026ndash;18.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e220.5 (78.0, 627.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e PET/CT, positron emission tomography/computed tomography; PAC, plasma aldosterone concentration; DRC, direct renin concentration; ARR, aldosterone/renin ratio.\u003c/p\u003e\u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eImaging characteristics of \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT in different prognosis of PA patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;36\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eClinical success\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eBiochemical success\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIncomplete\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003eIncomplete\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisual analysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnilateral positive lesions and contralateral negative lesions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28\u003c/p\u003e \u003cp\u003e(77.78%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26\u003c/p\u003e \u003cp\u003e(72.22%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(5.56%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e28\u003c/p\u003e \u003cp\u003e(77.78%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilateral positive lesions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003cp\u003e(22.22%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(5.56%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(16.67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e(11.11%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e(11.11%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSUV\u003csub\u003emax\u003c/sub\u003e of the lesions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.29\u0026thinsp;\u0026plusmn;\u0026thinsp;7.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.67\u0026thinsp;\u0026plusmn;\u0026thinsp;6.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.96\u0026thinsp;\u0026plusmn;\u0026thinsp;2.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15.73\u0026thinsp;\u0026plusmn;\u0026thinsp;6.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e6.13\u0026thinsp;\u0026plusmn;\u0026thinsp;1.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSUV\u003csub\u003emax\u003c/sub\u003e of the opposite lesions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.89\u0026thinsp;\u0026plusmn;\u0026thinsp;1.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.85\u0026thinsp;\u0026plusmn;\u0026thinsp;1.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.05\u0026thinsp;\u0026plusmn;\u0026thinsp;1.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.726\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.14\u0026thinsp;\u0026plusmn;\u0026thinsp;1.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e4.13\u0026thinsp;\u0026plusmn;\u0026thinsp;1.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.291\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSUV\u003csub\u003emax\u003c/sub\u003e of the liver\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.529\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.39\u0026thinsp;\u0026plusmn;\u0026thinsp;0.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e2.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.562\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDIR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.35\u0026thinsp;\u0026plusmn;\u0026thinsp;1.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.91\u0026thinsp;\u0026plusmn;\u0026thinsp;1.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.38\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.32\u0026thinsp;\u0026plusmn;\u0026thinsp;1.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e1.48\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLLR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.97\u0026thinsp;\u0026plusmn;\u0026thinsp;3.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.13\u0026thinsp;\u0026plusmn;\u0026thinsp;3.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.90\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.84\u0026thinsp;\u0026plusmn;\u0026thinsp;3.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e3.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e SUV\u003csub\u003emax\u003c/sub\u003e, the maximum standardized uptake value; DIR, dominant/inferior side uptake ratio; LLR, lesion/liver uptake ratio.\u003c/p\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eEfficacy of \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT for predicting surgical outcomes\u003c/h2\u003e \u003cp\u003eThe prognostic value of \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT was evaluated in the 36 surgically treated patients. Comparative analyses demonstrated that patients with complete clinical success had significantly higher SUV\u003csub\u003emax\u003c/sub\u003e values than those with incomplete success (17.67\u0026thinsp;\u0026plusmn;\u0026thinsp;6.27 vs. 6.96\u0026thinsp;\u0026plusmn;\u0026thinsp;2.01). Similarly, patients with complete biochemical success exhibited higher SUV\u003csub\u003emax\u003c/sub\u003e values than those with incomplete success (15.73\u0026thinsp;\u0026plusmn;\u0026thinsp;6.62 vs. 6.13\u0026thinsp;\u0026plusmn;\u0026thinsp;1.80). Additionally, the levels of DIR (3.91\u0026thinsp;\u0026plusmn;\u0026thinsp;1.65 vs. 1.38\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and LLR (8.13\u0026thinsp;\u0026plusmn;\u0026thinsp;3.23 vs. 2.90\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were significantly higher in the complete clinical success group compared to the incomplete success group. Similar trends were observed for biochemical success (DIR: 3.32\u0026thinsp;\u0026plusmn;\u0026thinsp;1.72 vs. 1.48\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; LLR: 6.84\u0026thinsp;\u0026plusmn;\u0026thinsp;3.03 vs. 3.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003ePredictive Performance of \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT Indicators\u003c/h2\u003e \u003cp\u003eThe sensitivity, specificity, and accuracy of \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT visual analysis for predicting complete clinical success were 92.86%, 75.00%, and 88.89%, respectively (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e4\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eA). ROC curve analysis identified an optimal SUV\u003csub\u003emax\u003c/sub\u003e cut-off value of 10.00 for complete clinical success, with an area under the curve (AUC) of 0.9063 (95% confidence interval [CI], 0.7949\u0026ndash;1.000, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0005). For DIR, the optimal cut-off was 1.613, with an AUC of 0.9598 (95% CI, 0.8873\u0026ndash;1.000, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), sensitivity of 90.32%, specificity of 87.50%, and accuracy of 90.32%. For LLR, the optimal cut-off was 4.575, with an AUC of 0.9777 (95% CI, 0.9352\u0026ndash;1.000, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), sensitivity of 85.71%, specificity of 100%, and accuracy of 88.89% (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e4\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eA).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe Predictive efficacy of \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT based on visual and semi-quantitative analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSensitivity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSpecificity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAccuracy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAUC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e95%CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical success\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisual analysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e92.86%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e88.89%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.8393\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.6510-1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.0038\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSUV\u003csub\u003emax\u003c/sub\u003e=10.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e85.71%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87.50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e86.11%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.9063\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.7949-1.0000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.0005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDIR\u0026thinsp;=\u0026thinsp;1.613\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e96.43%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87.50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e90.32%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.9598\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.8873-1.0000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLLR\u0026thinsp;=\u0026thinsp;4.575\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e85.71%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e88.89%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.9777\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.9352-1.0000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBiochemical success\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisual analysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e87.50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e88.89%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.9375\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.8577-1.0000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.0048\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSUV\u003csub\u003emax\u003c/sub\u003e=8.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e90.63%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e91.67%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.9453\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.8705-1.0000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.0041\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDIR\u0026thinsp;=\u0026thinsp;2.031\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e75.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e77.78%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.8203\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.6875\u0026ndash;0.9531\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.0390\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLLR\u0026thinsp;=\u0026thinsp;4.062\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e81.25%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e86.11%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.8984\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.7921-1.0000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.0103\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e SUV\u003csub\u003emax\u003c/sub\u003e, the maximum standardized uptake value; DIR, dominant/inferior side uptake ratio; LLR, lesion/liver uptake ratio.\u003c/p\u003e\u003cp\u003eWhen complete biochemical success was used as the endpoint, the sensitivity, specificity, and accuracy of visual analysis were 87.50%, 100%, and 88.89%, respectively (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e4\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eB). The optimal SUV\u003csub\u003emax\u003c/sub\u003e cut-off for complete biochemical success was 8.30, with an AUC of 0.9453 (95% CI, 0.8577\u0026ndash;1.000, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0048), sensitivity of 90.63%, specificity of 100%, and accuracy of 91.67%. For DIR, the optimal cut-off was 2.031, with an AUC of 0.8203 (95% CI, 0.6875\u0026ndash;0.9531, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0390), sensitivity of 75%, specificity of 100%, and accuracy of 77.78%. For LLR, the optimal cut-off was 4.062, with an AUC of 0.8984 (95% CI, 0.7921\u0026ndash;1.000, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0103), sensitivity of 81.25%, specificity of 100%, and accuracy of 86.11% (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e4\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eB).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003ePostoperative pathological results\u003c/h2\u003e \u003cp\u003ePostoperative pathological results were analyzed to explore factors contributing to better surgical outcomes in patients undergoing \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT. All these patients exhibited prominently positive CXCR4 staining. Among the 36 patients, 77.78% (28/36) were diagnosed with adrenocortical adenoma, showing positive CYP11B2 expression (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eA). Additionally, 8.33% (3/36) had adrenocortical adenomas without CYP11B2 expression but with significant CXCR4 expression (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eB). Conversely, 13.89% (5/36) were diagnosed with adrenocortical hyperplasia, with 3 showing positive CYP11B2 expression and 2 showing negative staining. All hyperplastic lesions exhibited mild CXCR4 expression (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eC-D). Overall, the consistency between CXCR4 and CYP11B2 expression was 86.11% (31/36).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eComparison between AVS and \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT\u003c/h2\u003e \u003cp\u003eIn our cohort, 5 patients underwent both successful AVS and \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT. The consistency between the two methods was 80% (4/5). Two patients showed concordant lateralization on both tests and achieved complete clinical and biochemical success, with pathological findings confirming CYP11B2-positive cortical adenomas. However, one patient exhibited unilateral lateralization on PET/CT but no dominant secretion on AVS; unilateral adrenalectomy resulted in clinical and biochemical success, with pathological confirmation of a CYP11B2-positive cortical adenoma. The remaining two patients showed no lateralization on either AVS or \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT test, resulting in medical treatment (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of AVS and \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT Imaging Results\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePatient\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eAVS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c7\" namest=\"c4\"\u003e \u003cp\u003e\u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePathological result\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCYP11B2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eBiochemical success\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eClinical success\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLateralization\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLateralization\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSUV\u003csub\u003emax\u003c/sub\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLLR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDIR\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eAdenoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eAdenoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eAdenoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c11\" namest=\"c8\"\u003e \u003cp\u003eMedical treatment\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c11\" namest=\"c8\"\u003e \u003cp\u003eMedical treatment\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\u003cp\u003e\u003cstrong\u003eAbbreviations:\u0026nbsp;\u003c/strong\u003eAVS, adrenal vein sampling; LI, lateralization index; L, left; B, bilateral; R, right.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis retrospective analysis demonstrates that surgical intervention guided by CXCR4-targeted \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT achieves favorable clinical and biochemical outcomes in PA patients with bilateral adrenal lesions. Parameters including visual analysis, SUV\u003csub\u003emax\u003c/sub\u003e, LLR, and DIR effectively identified surgical candidates, suggesting CXCR4-based functional imaging could circumvent the need for AVS in this complex subgroup. Precision and noninvasiveness diagnostics of disease is currently an emerging trend in the clinic. Our study proposes a paradigm shift toward CXCR4 PET/CT-guided surgery decision-making in AVS-free way for PA patients with bilateral adrenal lesions.\u003c/p\u003e \u003cp\u003eCurrent guidelines recommend using AVS as the gold standard for PA lateralization and treatment selection (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan additionalcitationids=\"CR28\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). However, technical limitations, inconsistent use criteria, and high failure rates hinder widespread adoption of AVS (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). Despite the introduction of AVS at our center in 2020, only 12 out of 51 (23.53%) PA patients with bilateral adrenal lesions successfully underwent AVS in this study. Notably, the 80% concordance between \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT and AVS lateralization in our study, coupled with superior surgical outcome prediction (100% vs. 67%), indicated the potential to replace AVS. Our results echo the reports from other investigators, in which the tests showed a 66.7% \u0026minus;\u0026thinsp;90% concordance rate and \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT was equal to or even better than AVS in predicting outcomes after surgery(\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Previous studies predominantly focused on unilateral PA patients, with only a small subset of patients with bilateral lesions included. Discrepancies among these studies could be attributed to variations in sample size and characteristics. Before considering revisions to the guidelines, further investigation is warranted to determine whether \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT can serve as a cost-effective, convenient, and non-invasive alternative to AVS.\u003c/p\u003e \u003cp\u003eMultiple studies have demonstrated the reliability of CXCR4-targeted functional imaging in identifying aldosterone-secreting nodules and classifying PA (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan additionalcitationids=\"CR17 CR18\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). For instance, Ding et al. reported that the SUVmax value of APAs (15.3\u0026thinsp;\u0026plusmn;\u0026thinsp;7.7) was significantly higher than that of suspected unilateral adrenal hyperplasia (UAH) (9.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7), IHA (4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3), and NFA (4.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7) (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Similarly, a previous study found a median SUV\u003csub\u003emax\u003c/sub\u003e value of 14.5 in APAs, which was notably higher than that of IHA (4.8) and NFA (4.65) (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). In our study, the average SUV\u003csub\u003emax\u003c/sub\u003e value of adrenal lesions selected for surgical removal was 15.30\u0026thinsp;\u0026plusmn;\u0026thinsp;7.18, underscoring the significant utility of \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT in guiding surgical decision-making for bilateral adrenal lesions by effectively identifying aldosterone-producing nodules such as APAs. This finding was further corroborated by postoperative pathological analysis. Notably, \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT demonstrated superior performance in identifying APAs with positive CYP11B2 expression (77.8%, 28/36). Our results support the high concordance rate between CXCR4 and CYP11B2 expression, as previously reported(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). However, two patients with CYP11B2-negative/CXCR4-positive adenomas still achieved biochemical remission, suggesting alternative aldosterone-secreting mechanisms linked to somatic mutations(\u003cspan additionalcitationids=\"CR33 CR34\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e), which this phenomenon warranted investigation into whether CXCR4 overexpression reflects latent autonomous secretion despite negative CYP11B2 staining.\u003c/p\u003e \u003cp\u003eEvidence from various studies has demonstrated the utility of several indicators of CXCR4-targeted \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT imaging\u0026mdash;such as visualization, LLR, and lesion-to-contralateral adrenal gland ratio (LCR)\u0026mdash;in distinguishing and predicting APAs (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan additionalcitationids=\"CR17 CR18\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). However, most of these studies prioritized pathological diagnosis and provided limited insights into prognosis. Recently, Ding et al. reported that \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT could differentiate surgically eligible from ineligible micronodules, primarily based on surgical pathology and outcomes (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Notably, all adrenal lesions analyzed in their study were smaller than 1 cm, with the majority being unilateral. To our knowledge, this is the first study to evaluate the efficacy of \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT in predicting surgical outcomes for PA patients with bilateral adrenal lesions, a scenario that poses greater complexity and challenges in clinical practice. Our findings suggest that visual assessment of \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT images and semiquantitative analysis of PET data may be sufficient to predict adrenalectomy outcomes in PA patients with bilateral adrenal lesions with high accuracy. Specifically, patients diagnosed with lateralized disease, characterized by unilateral positive or asymmetrically bilateral positive lesions, may benefit from the removal of the affected adrenal gland. Interestingly, unlike previous studies focused on identifying APAs, the application of semiquantitative analysis of \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET data to predict surgical outcomes may require a relatively higher SUV\u003csub\u003emax\u003c/sub\u003e cut-off value. This discrepancy may be partially attributed to the complexity of predicting PA prognosis. In fact, surgical outcomes in PA patients are influenced not only by pathological classification but also by confounding factors such as primary hypertension and comorbidities like chronic renal failure, which warrant further investigation (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThis study has several limitations. First, its retrospective nature and single-center design may have introduced selection bias and influenced the findings. Second, the limited sample size, resulting from our focus on bilateral adrenal lesions, might have led to insufficient statistical significance and biased outcomes. Third, although high-resolution adrenal CT was used to initially detect bilateral adrenal lesions, some microadenomas or smaller lesions might have been missed. Additionally, most tumor lesions in our study were \u0026ge;\u0026thinsp;1 cm in diameter, which hindered the analysis of the diagnostic efficacy of PET/CT for nodules smaller than 1 cm, potentially introducing uncertainty into our results. Importantly, since most patients declined the AVS test, we could not assess the potential of false negative results of \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT, which may influence treatment decisions. Furthermore, the majority of treatment decisions in this study were based on \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT without AVS, which may represent another potential source of bias. Therefore, we emphasize the need for a large-scale, prospective, randomized, controlled, multicenter trial to further validate the applicability of \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT as an alternative to AVS in guiding surgical treatment for PA patients.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, this retrospective study demonstrates that CXCR4-targeted \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT can be effectively utilized for surgical decision-making in PA patients with bilateral adrenal lesions, providing a potential alternative to AVS for prognostic prediction. This study lays a solid foundation for future randomized controlled trials comparing \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT with AVS in patients with PA and bilateral adrenal lesions.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u0026nbsp;\u003c/strong\u003eWe thank the MJ Language Editing Services (https://www.mjeditor.com) for its linguistic assistance during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u0026nbsp;\u003c/strong\u003eAll authors contributed to the study conception and design and commented on previous versions of the manuscript. All authors read and approved the final manuscript. The contributions of every author are as follows: conceptualization: Yu Gan, Longfei Liu, Kai Cheng; data curation: Zhiwei Shu, Yao He, Min Guo, Zhuying Xia, Xiaodan Fu, Bingsheng Li, Bo Zhang, Yi Yang, Jiaxian Chen; PET imaging acquisition: Tingting Long; formal analysis: Zhiwei Shu, Yao He; Writing-original draft: Zhiwei Shu, Yao He; Writing-review \u0026amp; editing: Tiejian Jiang, Xiang Chen, Yu Gan, Longfei Liu, Kai Cheng; funding acquisition: Yu Gan, Longfei Liu.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis study was funded by National Natural Science Foundation of China (82273121), Hunan Natural Science Foundation (2022JJ20096), and National Research Center for Clinical Medicine of Geriatric Diseases Clinical Research Fund (2022LNJJ12).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability:\u0026nbsp;\u003c/strong\u003eThe datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eThis study was approved by the ethics committee of the Xiangya Hospital, Central South University (2023111517). This article does not contain any experiments with animals. Informed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eWritten informed consent was obtained from the patient for publication of this study and accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate: Competing interests:\u0026nbsp;\u003c/strong\u003eThe authors have no competing interests to disclose in relation with this article\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eChoy KW, Fuller PJ, Russell G, Li Q, Leenaerts M, Yang J. Primary aldosteronism. BMJ (Clinical Res ed). 2022;377:e065250.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMonticone S, D'Ascenzo F, Moretti C, Williams TA, Veglio F, Gaita F, et al. 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J Clin Endocrinol Metab. 2016;101(5):1889\u0026ndash;916.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBurrello J, Burrello A, Pieroni J, Sconfienza E, Forestiero V, Amongero M, et al. Prediction of hyperaldosteronism subtypes when adrenal vein sampling is unilaterally successful. Eur J Endocrinol. 2020;183(6):657\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRossi GP, Barisa M, Allolio B, Auchus RJ, Amar L, Cohen D, et al. The Adrenal Vein Sampling International Study (AVIS) for identifying the major subtypes of primary aldosteronism. J Clin Endocrinol Metab. 2012;97(5):1606\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRossi GP. Primary Aldosteronism: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019;74(22):2799\u0026ndash;811.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWilliams TA, Gong S, Tsurutani Y, Tezuka Y, Thuzar M, Burrello J, et al. 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Br J Radiol. 2022;95(1136):20211272.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGao Y, Ding J, Cui Y, Li T, Sun H, Zhao D, et al. Functional nodules in primary aldosteronism: identification of CXCR4 expression with (68)Ga-pentixafor PET/CT. Eur Radiol. 2023;33(2):996\u0026ndash;1003.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHu J, Xu T, Shen H, Song Y, Yang J, Zhang A, et al. Accuracy of Gallium-68 Pentixafor Positron Emission Tomography-Computed Tomography for Subtyping Diagnosis of Primary Aldosteronism. JAMA Netw open. 2023;6(2):e2255609.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDing J, Tong A, Zhang Y, Wen J, Zhang H, Hacker M, et al. Functional Characterization of Adrenocortical Masses in Nononcologic Patients Using (68)Ga-Pentixafor. J Nucl Med. 2022;63(3):368\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDing J, Li X, Liu S, Gao Y, Zheng G, Hacker M, et al. Clinical Value of (68)Ga-Pentixafor PET/CT in Subtype Diagnosis of Primary Aldosteronism Patients with Adrenal Micronodules. Journal of nuclear medicine: official publication. Soc Nuclear Med. 2024;65(1):117\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDing J, Tong A, Zhang Y, Wen J, Huo L. Intense 68Ga-Pentixafor Activity in Aldosterone-Producing Adrenal Adenomas. Clin Nucl Med. 2020;45(4):336\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZheng Y, Long T, Peng N, Zhen M, Ye Q, Zhang Z, et al. The Value of Targeting CXCR4 With 68Ga-Pentixafor PET/CT for Subtyping Primary Aldosteronism. J Clin Endocrinol Metab. 2023;109(1):171\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYin X, Ai K, Luo J, Liu W, Ma X, Zhou L, et al. A comparison of the performance of (68)Ga-Pentixafor PET/CT versus adrenal vein sampling for subtype diagnosis in primary aldosteronism. Front Endocrinol. 2024;15:1291775.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYi T, Lu D, Cui Y, Zhang Z, Yang X, Zhang J et al. (68)Ga-pentixafor PET/CT Is a Supplementary Method for Primary Aldosteronism Subtyping Compared with Adrenal Vein Sampling. Molecular imaging and biology. 2024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZuo R, Liu S, Ren X, Li W, Xia Z, Xu L, et al. Typing diagnostic value of (68)Ga-pentixafor PET/CT for patients with primary aldosteronism and unilateral nodules. Endocrine. 2025;87(1):314\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZuo R, Liu S, Li W, Xia Z, Xu L, Pang H. Clinical value of (68)Ga-pentixafor PET/CT in patients with primary aldosteronism and bilateral lesions: preliminary results of a single-centre study. EJNMMI Res. 2024;14(1):61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWilliams TA, Lenders JWM, Mulatero P, Burrello J, Rottenkolber M, Adolf C, et al. Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort. lancet Diabetes Endocrinol. 2017;5(9):689\u0026ndash;99.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu J, Tian W, Zhang L, Zhang J, Zhou B. Assessing the quality of guidelines for primary aldosteronism: which guidelines are worth applying in diverse settings? J Hypertens. 2019;37(7):1500\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMulatero P, Bertello C, Rossato D, Mengozzi G, Milan A, Garrone C, et al. Roles of clinical criteria, computed tomography scan, and adrenal vein sampling in differential diagnosis of primary aldosteronism subtypes. J Clin Endocrinol Metab. 2008;93(4):1366\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLim V, Guo Q, Grant CS, Thompson GB, Richards ML, Farley DR, et al. Accuracy of adrenal imaging and adrenal venous sampling in predicting surgical cure of primary aldosteronism. J Clin Endocrinol Metab. 2014;99(8):2712\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDekkers T, Prejbisz A, Kool LJS, Groenewoud H, Velema M, Spiering W, et al. Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcome-based randomised diagnostic trial. lancet Diabetes Endocrinol. 2016;4(9):739\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee SE, Park SW, Choi MS, Kim G, Yoo JH, Ahn J, et al. Primary aldosteronism subtyping in the setting of partially successful adrenal vein sampling. Therapeutic Adv Endocrinol metabolism. 2021;12:2042018821989239.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZheng Y, Long T, Peng N, Zhen M, Ye Q, Zhang Z et al. The Value of Targeting CXCR4 with 68Ga-Pentixafor PET/CT for Subtyping Primary Aldosteronism. J Clin Endocrinol Metab. 2023.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDe Sousa K, Boulkroun S, Baron S, Nanba K, Wack M, Rainey WE, Genetic, Cellular, and Molecular Heterogeneity in Adrenals With Aldosterone-Producing Adenoma., Hypertension et al. Dallas, Tex: (1979). 2020;75(4):1034-44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMonticone S, Castellano I, Versace K, Lucatello B, Veglio F, Gomez-Sanchez CE, et al. Immunohistochemical, genetic and clinical characterization of sporadic aldosterone-producing adenomas. Mol Cell Endocrinol. 2015;411:146\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDekkers T, ter Meer M, Lenders JW, Hermus AR, Schultze Kool L, Langenhuijsen JF, et al. Adrenal nodularity and somatic mutations in primary aldosteronism: one node is the culprit? J Clin Endocrinol Metab. 2014;99(7):E1341\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBurrello J, Burrello A, Stowasser M, Nishikawa T, Quinkler M, Prejbisz A, et al. The Primary Aldosteronism Surgical Outcome Score for the Prediction of Clinical Outcomes After Adrenalectomy for Unilateral Primary Aldosteronism. Ann Surg. 2020;272(6):1125\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"ejnmmi-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejre","sideBox":"Learn more about [EJNMMI Research](http://ejnmmires.springeropen.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ejre/default.aspx","title":"EJNMMI Research","twitterHandle":"@officialEANM","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"68Ga-pentixafor PET/CT, CXCR4, primary aldosteronism, surgery decision-making, bilateral adrenal lesions","lastPublishedDoi":"10.21203/rs.3.rs-6385295/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6385295/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eFor patients diagnosed with primary aldosteronism accompanied by bilateral adrenal lesions, identifying optimal candidates for surgical intervention remains a significant clinical challenge. Although adrenal venous sampling (AVS) is currently the gold standard for lateralizing aldosterone hypersecretion, its technical complexity, invasiveness, and interpretive difficulties restrict its widespread adoption. In this study, we aimed to investigate the clinical application of \u003csup\u003e68\u003c/sup\u003eGa-pentixafor positron emission tomography/computed tomography (PET/CT) as a non-invasive imaging modality in AVS-free surgical decision-making for PA patients with bilateral adrenal lesions.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eAmong the 51 patients who underwent \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT, 36 patients had adrenalectomy, with the surgical side determined by PET/CT lateralization. The postoperative complete biochemical and clinical success rates for these patients were 91.67% and 100%, respectively, Additionally, receiver operating characteristic curve analysis indicated that PET/CT results were favorable predictors of postoperative outcomes in surgical patients. Postoperative pathological evaluation of \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT-guided surgical patients revealed that 86.11% had adrenocortical adenomas with positive CYP11B2 and CXCR4 expression.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e \u003cp\u003eCXCR4-targeted \u003csup\u003e68\u003c/sup\u003eGa-pentixafor PET/CT can be effectively utilized in surgical decision-making for PA patients with bilateral adrenal lesions, offering a potential alternative to AVS and may applied to predict postoperative biochemical and clinical success.\u003c/p\u003e\u003cp\u003e\u003cb\u003eTrial registration\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003csup\u003e68\u003c/sup\u003eGa-Pentixafor PET/CT for Guiding Surgical Treatment of Primary Aldosteronism With Bilateral Adrenal Lesions; Trial registration number: NCT06247566; Date of registration: 2021-11-01; URL of trial registry record: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://clinicaltrials.gov/study/NCT06247566\u003c/span\u003e\u003cspan address=\"https://clinicaltrials.gov/study/NCT06247566\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/p\u003e","manuscriptTitle":"Is CXCR4-Targeted 68Ga-Pentixafor PET/CT a Reliable AVS-free Modality for Surgical Decision-making and Prognostic Prediction in Primary Aldosteronism with Bilateral Adrenal Lesions?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-08 14:56:15","doi":"10.21203/rs.3.rs-6385295/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-05-11T07:20:08+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-25T09:23:33+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-11T15:17:51+00:00","index":"","fulltext":""},{"type":"submitted","content":"EJNMMI Research","date":"2025-04-11T10:12:48+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"ejnmmi-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejre","sideBox":"Learn more about [EJNMMI Research](http://ejnmmires.springeropen.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ejre/default.aspx","title":"EJNMMI Research","twitterHandle":"@officialEANM","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a1bca288-a12e-4410-be93-156299d96f1c","owner":[],"postedDate":"May 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-09-01T16:09:36+00:00","versionOfRecord":{"articleIdentity":"rs-6385295","link":"https://doi.org/10.1186/s13550-025-01309-4","journal":{"identity":"ejnmmi-research","isVorOnly":false,"title":"EJNMMI Research"},"publishedOn":"2025-08-28 15:57:57","publishedOnDateReadable":"August 28th, 2025"},"versionCreatedAt":"2025-05-08 14:56:15","video":"","vorDoi":"10.1186/s13550-025-01309-4","vorDoiUrl":"https://doi.org/10.1186/s13550-025-01309-4","workflowStages":[]},"version":"v1","identity":"rs-6385295","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6385295","identity":"rs-6385295","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}