Split Renal Function Estimation Using [18F]F-Flotufolastat PET/CT: Comparison with [68Ga]Ga-PSMA-11 and [99mTc]Tc-MAG3 Scintigraphy

Split Renal Function Estimation Using [18F]F-Flotufolastat PET/CT: Comparison with [68Ga]Ga-PSMA-11 and [99mTc]Tc-MAG3 Scintigraphy | 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 Split Renal Function Estimation Using [ 18 F]F-Flotufolastat PET/CT: Comparison with [ 68 Ga]Ga-PSMA-11 and [ 99m Tc]Tc-MAG3 Scintigraphy Michael Christian Marius Gammel, Charlotte Olufs, Kimberley Hansen, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7528938/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 03 Feb, 2026 Read the published version in EJNMMI Research → Version 1 posted 5 You are reading this latest preprint version Abstract Background: Physiological prostate-specific membrane antigen (PSMA) expression in renal proximal tubules results in radiopharmaceutical uptake in PSMA-PET, suggesting the potential to assess renal function. Thus, we evaluated whether PSMA-PET/CT allowed estimation of split renal function (SRF), potentially replacing [ 99m Tc]Tc-MAG3 scintigraphy. We retrospectively analyzed 302 patients with metastatic castration-resistant prostate cancer undergoing PSMA-PET/CT using either [ 18 F]F-flotufolastat ([ 18 F]F-rhPSMA-7.3) (n=221) or [ 68 Ga]Ga-PSMA-11 (n=81), along with [ 99m Tc]Tc-MAG3 scintigraphy, prior to PSMA radioligand therapy. SRF was calculated from PSMA-PET/CT using mean standardized uptake values and CT-derived renal volumes. SRF was calculated from [ 99m Tc]Tc-MAG3 using standard integral analysis. Correlations between PET-derived SRF (PET-SRF) and [ 99m Tc]Tc-MAG3 -derived SRF ([ 99m Tc]Tc-MAG3-SRF) were assessed using Pearson correlation and Bland–Altman analysis. Receiver operating characteristic (ROC) analyses were conducted to evaluate diagnostic performance in detecting impaired renal function (SRF ≤ 25% and ≤40%). A PET-based accumulation index (ACI) was explored for correlation with estimated glomerular filtration rate (eGFR). Results: Strong correlations were found between PET-SRF and [ 99m Tc]Tc-MAG3-SRF (r=0.88 for [ 18 F]F-flotufolastat, r=0.85 for [ 68 Ga]Ga-PSMA-11; both p<0.0001). Bland–Altman analysis showed a smaller mean bias and narrower limits of agreement for [ 18 F]F-flotufolastat (-0.56%; -11.88% to +10.75%) compared with [ 68 Ga]Ga-PSMA-11 (-1.18%; -15.3% to +12.95%), with 92% versus 83% of values within ± 10%, respectively. ROC analysis confirmed excellent accuracy for identifying [ 99m Tc]Tc-MAG3-SRF ≤ 25% (area under the curve [AUC] = 0.997 for [ 18 F]F-flotufolastat; AUC = 0.942 for [ 68 Ga]Ga-PSMA-11). ACI and eGFR were not significantly correlated (Spearman’s ρ=0.048; p=0.49]). Conclusion: PSMA-PET/CT provides reliable estimates of SRF, with [ 18 F]F-flotufolastat showing slightly superior agreement with [ 99m Tc]Tc-MAG3 scintigraphy. This may potentially eliminate the need for additional renal scintigraphy for SRF assessment in the future and may simplify workflows and reduce patient burden. Split renal function PSMA [99mTc]Tc-MAG3 prostate cancer PET/CT Figures Figure 1 Figure 2 Figure 3 Figure 4 INTRODUCTION Prostate cancer is one of the most common malignancies in men ( 1 ), requiring precise diagnostic and therapeutic approaches, particularly in advanced stages. Prostate-specific membrane antigen (PSMA) has emerged as a critical target in prostate cancer management due to its overexpression in malignant prostate tissue ( 2 ). Imaging with [ 68 Ga]- or [ 18 F]-labeled PSMA-targeted radiopharmaceuticals plays a pivotal role in staging, restaging, and monitoring response to therapy ( 3 – 9 ). Additionally, PSMA-targeted radioligand therapy (RLT) with [ 177 Lu]Lutetium-labeled PSMA (LuPSMA) radioligands has become an essential life-prolonging treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC) ( 10 ). Despite its specificity for prostate cancer cells, PSMA is also physiologically expressed in the proximal tubule cells of the kidneys ( 11 – 15 ). This renal uptake introduces a potential risk of radiation nephrotoxicity during PSMA-RLT ( 16 , 17 ). However, its presence also provides an opportunity to evaluate renal function non-invasively using PSMA-PET. The assessment of renal function is critical for prostate patients prior to therapeutic interventions (e.g. external beam radiation therapy, LuPSMA RLT) to minimize toxicity and optimize treatment planning ( 18 ). Until now, dynamic renal scintigraphy using Technetium-99m [ 99m Tc]Tc-mercapto-acetyltriglycine ([ 99m Tc]Tc-MAG3) remains the clinical standard for assessing global and split renal function (SRF) and excluding urinary outflow obstruction. [ 99m Tc]Tc-MAG3 scintigraphy accurately estimates tubular renal function but requires an additional imaging procedure, which can be time-consuming and burdensome, particularly for patients with painful skeletal metastases. Previous preliminary studies have demonstrated a strong correlation between PSMA-PET-derived SRF and [ 99m Tc]Tc-MAG3-based SRF using [ 68 Ga]Ga-PSMA-11 and [ 18 F]F-PSMA-1007 ( 19 – 21 ). However, these studies have been limited by relatively small patient populations (n = 28–97). 18 F- Flotufolastat ([ 18 F]F-rhPSMA-7.3), is a recently FDA-approved radiohybrid PSMA-PET radiopharmaceutical for staging and restaging of prostate cancer ( 22 , 23 ) but has not yet been investigated in assessing renal function. In this study, we retrospectively evaluated a large cohort of patients with mCRPC who underwent both PSMA-PET and [ 99m Tc]Tc-MAG3 scintigraphy. We aimed to compare the accuracy of SRF derived using [ 68 Ga]Ga-PSMA-11 and [ 18 F]F-flotufolastat versus the standard [ 99m Tc]Tc-MAG3 scintigraphy. Additionally, we investigated correlations between absolute renal uptake derived from PSMA-PET, tubular excretion rate (TER) of [ 99m Tc]Tc-MAG3, and serum creatinine levels to explore global renal function parameters. MATERIALS AND METHODS Patient Characteristics This retrospective study included 302 patients with advanced mCRPC who underwent either [ 68 Ga]Ga-PSMA-11 PET/CT (n = 81) or [ 18 F]F-flotufolastat (n = 221) and [ 99m Tc]Tc-MAG3 scintigraphy as part of their clinical evaluation for PSMA RLT at the, Technical University of Munich University Hospital, Germany. All patients provided written informed consent for the clinical examination and reported investigations were conducted in accordance with the Declaration of Helsinki and with national regulations. The local ethics committee approved the retrospective analysis (permits: 2019-99_2-S-SR, updated on May 31, 2023). All patients evaluated for RLT between October 2014 and October 2022 were included, with a median interval of 15 days between PSMA-PET and [ 99m Tc]Tc-MAG3 scintigraphy. Patient characteristics are summarized in Table 1 . Table 1 Patient characteristics Characteristic All patients (N = 302) Patients who underwent [ 68 Ga]Ga-PSMA-11 PET/CT, n 81 Patients who underwent [ 18 F]F-flotufolastat PET/CT, n 221 Age, years 72 ± 10 Injected activity [ 18 F]F-flotufolastat, MBq 288 ± 60 Injected activity [ 68 Ga]Ga-PSMA-11, MBq 122 ± 36 Acquisition p.i. [ 18 F], minutes 72 ± 13 Acquisition p.i. [ 68 Ga], minutes 56 ± 12 TER, mL/min 201 ± 46 Creatinine, mg/dL 1.0 ± 0.29 eGFR, mL/min/1.73 m 2 77 ± 19 Patients with eGFR > 60 ml/min, n 228 Patients with eGFR ≤ 60 ml/min, n 74 Split function, % 50 ± 12 PSA mean , ng/mL 338 ± 700 Unless otherwise stated, all values are mean ± SD. 68 Ga = Gallium-68; PSMA = prostate-specific membrane antigen; PET = positron emission tomography; CT = computed tomography; 18 F = Fluorine-18; rh = radiohybrid; MBq = megabecquerel; TER = tubular excretion rate; eGFR = estimated glomerular filtration rate, PSA = prostate-specific antigen. [ 18 F]F-flotufolastat PET/CT and [ 68 Ga]Ga-PSMA-11 PET/CT The radiolabeling of both [ 18 F]F-flotufolastat and [ 68 Ga]Ga-PSMA-11 followed established protocols described in previous studies ( 24 )( 25 ). For [ 18 F]F-flotufolastat, an intravenous bolus of 288 ± 60 MBq was administered, and PET scanning commenced approximately 72 ± 13 minutes post injection. For [ 68 Ga]Ga-PSMA-11, a mean activity of 122 ± 36 MBq was injected intravenously, with PET scanning commencing at a mean of 56 ± 12 minutes post-injection. All patients received a diluted oral contrast medium (300 mg Telebrix, Guerbet) and a diagnostic CT scan in the portal venous phase, performed 80 seconds after intravenous administration of iodinated contrast (Imeron 300, Bracco Imaging). PET/CT scans for both [ 18 F]F-flotufolastat and [ 68 Ga]Ga-PSMA-11were conducted using either a Siemens Biograph mCT Flow or Siemens Biograph Vision 600 scanner (Siemens Healthineers. Imaging was performed in 3D mode, with acquisition speeds of 0.8 mm/s (Biograph mCT Flow) and 1.1 mm/s (Biograph Vision 600) for [ 18 F]F-flotufolastat, and 1.1–1.5 mm/second or 3–4 minutes per bed position for [ 68 Ga]Ga-PSMA-11. Reconstruction was carried out using ordered-subset expectation maximization (TrueX, 4 iterations, 8 subsets) for both radiopharmaceuticals. A Gaussian smoothing filter of 2 mm (full width at half maximum) was applied for [ 18 F]F-flotufolastat, and 5 mm (full width half maximum) for [ 68 Ga]Ga-PSMA-11. Emission data were corrected for randoms, dead time, scatter, and attenuation for both protocols, ensuring consistent and accurate quantitative analysis. SRF from PSMA-PET SRF was calculated using PET data based on renal uptake of regions of interest (ROI) were delineated using 50% isocontour thresholds to extract both maximum standardized uptake value (SUV max ) and mean standardized uptake value (SUV mean ). For PET, ROIs were manually drawn over the kidneys, excluding the renal pelvic caliceal system (RPCS). On CT, the renal parenchyma was defined while excluding the renal pelvic caliceal system and cystic structures. The SRF was calculated using the following formula: Calculations were performed separately using SUV max and SUV mean , with volumes derived from either PET (functional) or CT (anatomical) data. All ROI placements and analyses were reviewed by an experienced nuclear medicine physician (I.R.) to ensure consistency and accuracy. Calculation and Statistical Evaluation of the PET-Based Accumulation Index (ACI) To explore potential associations between PSMA-PET-derived measures and global renal function, an Accumulation Index (ACI) was calculated for each patient by dividing the combined renal parenchymal volume (segmented from CT) by the sum of the SUV mean estimates from both kidneys. This approach was inspired by the methodology proposed by Weissinger et al. for somatostatin receptor targeted PET/CT imaging, where the ACI showed strong positive correlation with MAG3-derived renal function parameters ( 26 ). Although PSMA tracers differ substantially in their pharmacokinetics, particularly regarding proximal tubular binding, we considered this concept worth exploring in our cohort. Due to non-normal distribution of ACI and estimated glomerular filtration rate (eGFR) (Shapiro–Wilk test, p < 0.0001 for both), correlations were assessed using Spearman’s rank correlation coefficient (ρ). Analyses were performed separately for [ 18 F]F-flotufolastat and [ 68 Ga]Ga-PSMA-11. [ 99m Tc]Tc-MAG3-Scintigraphy To ensure optimal hydration, all patients were instructed to drink at least 10 mL of mineral water per kilogram of bodyweight 30 minutes prior to scintigraphy. Dynamic renal scintigraphy with [ 99m Tc]Tc-MAG3 was performed per European Association of Nuclear Medicine guidelines ( 27 ) and the Bubeck method ( 28 ), using approximately 100 MBq of [ 99m Tc]Tc-MAG3 and planar dynamic imaging with both posterior and anterior detectors for 20 minutes. Current CT images were used to determine whether calculation of the geometric mean was required. ROI were drawn manually over the renal parenchyma, including the renal pelvic caliceal system, as well as the aorta and background regions. In cases of inadequate[ 99m Tc]Tc-MAG3 excretion observed in post-micturition images, furosemide was administered, followed by an additional 20 minutes of imaging. SRF was calculated from renal activity curves between 60–100 seconds. Tubular extraction rate (TER) was determined using the two-sample plasma clearance method, and side-separated TER was calculated by multiplying SRF with the total TER. Statistical Analysis All statistical analyses were performed using Microsoft Excel and MedCalc version 23.1.3 (MedCalc Software Ltd, Ostend, Belgium). Continuous variables were expressed as mean ± standard deviation. Normality was assessed using the Shapiro–Wilk test. The Pearson correlation coefficient (r) was calculated to evaluate the linear relationship between PSMA-PET-derived SRF(PET-SRF) and [ 99m Tc]Tc-MAG3-derived SRF ([ 99m Tc]Tc-MAG3-SRF) as the reference standard. In addition, correlations between PET-based measures of absolute renal uptake and TER were assessed to evaluate global renal function. Bland–Altman analysis ( 29,30 ) was conducted to assess agreement between methods, including the calculation of mean differences, limits of agreement, and the proportion of values within a predefined range of ± 10 %. Linear regression analysis was performed to model the relationship between PET-SRF and [ 99m Tc]Tc-MAG3-SRF, with coefficients of determination (R 2 ), regression equations, and residual analyses reported. Normality of residuals was tested using the D'Agostino–Pearson test. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic accuracy of PET-SRF for identifying severely impaired renal function ([ 99m Tc]Tc-MAG3-SRF ≤ 25 %) and reduced renal function ([ 99m Tc]Tc-MAG3-SRF ≤ 40 %). The area under the ROC curve (AUC), sensitivity, specificity, and optimal thresholds based on the Youden Index were reported. Statistical significance was set at p<0.05. RESULTS Renal function parameters were within an overall preserved range, with a mean serum creatinine of 1.0 ± 0.29 mg/dL and mean eGFR of 77 ± 19 mL/min/1.73 m². A total of 228 (75%) patients presented with an eGFR above 60 mL/min. Mean TER was 201 ± 46 mL/min. Mean SRF based on [ 99m Tc]Tc-MAG3 was 50 ± 12%. SRF Correlation Between PET- and [ 99m Tc]Tc-MAG3 -Derived SRF A strong linear relationship was observed across all tested PET SRF combinations (SUV max and SUV mean , volumes derived from PET or CT) and [ 99m Tc]Tc-MAG3-SRF, with Pearson correlation coefficients (r) ranging from 0.835 to 0.881 (all p<0.0001). The best agreement was achieved using SUV mean in combination with CT-based renal volumes (r = 0.881), therefore all subsequent analyses were performed using this approach. Table 2 summarizes the findings of the ¹⁸F-flotufolastat analysis. Table 2 . Methods for SRF calculation using ¹⁸F-flotufolastat Methods for SRF-calculation using ¹⁸F-flotufolastat Pearson r p -value [ 99m Tc]Tc-MAG3 -SRF & SRF(SUV mean , CT-Volume) 0.881 < 0.0001 [ 99m Tc]Tc-MAG3 -SRF & SRF(SUV max , CT-Volume) 0.878 < 0.0001 [ 99m Tc]Tc-MAG3 -SRF & SRF(SUV max , PET-Volume) 0.849 < 0.0001 [ 99m Tc]Tc-MAG3 -SRF & SRF(SUV mean , PET-Volume) 0.835 < 0.0001 SRF = split renal function; 18 F = Fluorine-18; rh = radiohybrid; PSMA = prostate-specific membrane antigen; MAG3 = mercapto-acetyltriglycine, SUV mean = mean standardized uptake value; CT = computed tomography; SUV max = maximum standardized uptake value; PET = positron emission tomography; ⁹⁹ᵐTc = Technetium-99m. Agreement Between PET- and [ 99m Tc]Tc-MAG3 -SRF Estimates Bland–Altman analysis revealed no significant systematic bias for either radiopharmaceutical. For [ 68 Ga]Ga-PSMA-11, the mean difference between PET-SRF and [ 99m Tc]Tc-MAG3-SRF was -1.18% ( p = 0.15), with limits of agreement ranging from -15.30 % to 12.95 %. Additionally, 83% of values were within ± 10% of agreement. For [ 18 F]F-flotufolastat, the mean difference was slightly smaller at -0.56% (p=0.15), with narrower limits of agreement (-11.88% to +10.75%) and a higher proportion of values (92%) falling within ± 10%. (Figure 1) Modeling the Relationship Between PET- and [ 99m Tc]Tc-MAG3 -SRF The relationship between PET-SRF and [ 99m Tc]Tc-MAG3-SRF was modeled using linear regression. For [ 68 Ga]Ga-PSMA-11, the linear regression model produced an R 2 -value of 0.703, with the equation y = −0.1513 + 1.2763x (Figure 2). The slope (β1 = 1.2763) significantly deviated from 1 ( p < 0.0001), suggesting a slight overestimation of higher SRF values by PET. By comparison, [ 18 F]F-flotufolastat showed a stronger fit, with an R 2 -value of 0.7738 and the regression equation y = 0.1536 + 0.7020x (Figure 3). The slope (β1 = 0.7020) also significantly deviated from 1 (p<0.0001), indicating a slight underestimation. However, residuals for [ 18 F]F-flotufolastat were not normally distributed (p<0.0001, D’Agostino–Pearson test), potentially limiting the model's validity for extreme values. An overview of both regression models is provided in Table 3. Table 3 . Linear regression models for estimating [ 99m Tc]Tc-MAG3-SRF from PET-SRF values Radioligand R² Regression equation Slope (β₁) ≠ 1 (p) Intercept (β₀) Residuals normally distributed (p) ⁶⁸Ga-PSMA-11 0.703 y = −0.1513 + 1.2763x 0.05) ¹⁸F-flotufolastat 0.774 y = 0.1536 + 0.7020x < 0.0001 0.1536 no ( p < 0.0001) MAG3 = mercapto-acetyltriglycine; SRF = split renal function; PET = positron emission tomography; R 2 = coefficient of determination; 68 Ga = Gallium-68; PSMA = prostate-specific membrane antigen; 18 F = Fluorine-18; ⁹⁹ᵐTc = Technetium-99m. Diagnostic Accuracy of PET-SRF to Detect Functional Impairment The ROC analysis confirmed the excellent diagnostic performance of both [ 68 Ga]Ga-PSMA-11 and [ 18 F]F-flotufolastatin distinguishing impaired split renal function at thresholds of [ 99m Tc]Tc-MAG3-SRF ≤ 25% and ≤ 40%. At the 25 % threshold, [ 68 Ga]Ga-PSMA-11 achieved an AUC of 0.942 (95 % CI: 0.866–0.982; p<0.0001), with a sensitivity of 84% and a specificity of 100%. [ 18 F]F-flotufolastat demonstrated a slightly superior performance with an AUC of 0.997 (95 % CI: 0.978–1.000; p<0.0001), achieving a sensitivity of 98% and a specificity of 100%. At the 40% threshold, [ 68 Ga]Ga-PSMA-11 showed an AUC of 0.979 (95 % CI: 0.920–0.998; p<0.0001), with a sensitivity of 89% and a specificity of 100%. Similarly, [ 18 F]F-flotufolastatachieved an AUC of 0.954 (95 % CI: 0.917–0.978; p<0.0001), with a sensitivity of 90% and a specificity of 90%. (Figure 4) Assessment of Global Renal Function Using the PET-Based ACI The ACI showed a non-normal distribution with pronounced right skew and kurtosis (Shapiro–Wilk p < 0.0001). The mean eGFR in the overall cohort was 77 ± 19 mL/min/1.73 m². For patients who underwent [ 18 F]F-flotufolastatPET/CT (n=212), no significant correlation was observed between ACI and eGFR (Spearman’s ρ = 0.056 [p=0.414]). Similarly, in the [ 68 Ga]Ga-PSMA-11 subgroup (n=79), no significant association was found (Spearman’s ρ = –0.071 [ p = 0.536]). DISCUSSION Renal function is a critical factor for many prostate cancer therapies, including [ 177 Lu]Lu-PSMA therapy, and PSMA-PET/CT offers the potential advantage of calculating SRF as part of every routine scan. Previous studies have explored various radiopharmaceuticals in small cohorts as proof-of-concept investigations (n = 28–97) ( 19-21 ). To the best of our knowledge, this is the first study to directly compare [ 18 F]F-flotufolastatwith [ 68 Ga]Ga-PSMA-11 against [ 99m Tc]Tc-MAG3 renal scintigraphy, and to do so in a large patient cohort. This study demonstrated a strong correlation (see Table 2) between PSMA-PET-derived SRF and [ 99m Tc]Tc-MAG3-based SRF for both radiopharmaceuticals, with [ 18 F]F-flotufolastatexhibiting a slightly superior diagnostic performance due to its narrower limits of agreement and higher sensitivity. The strong correlations with [ 99m Tc]Tc-MAG3 observed in this study (r = 0.85 for [ 68 Ga]Ga-PSMA-11 and r = 0.88 for [ 18 F]F-flotufolastat) are in line with prior PSMA PET studies, which reported correlation coefficients between r = 0.85 and r = 0.96 for SRF estimation compared to MAG3 scintigraphy. For example, Rosar et al. found r = 0.91 for [ 68 Ga]Ga-PSMA-11, Gabela et al. reported r = 0.96 for the same tracer, and Rassek et al. demonstrated r = 0.87 for [ 18 F]F-PSMA-1007 ( 31-34 ). Notably, [ 99m Tc]Tc-DMSA scintigraphy achieves similar correlation coefficients for SRF when compared to MAG3 or DTPA-based methods, typically in the range of r = 0.82–0.99 ( 35-38 ). A compact overview of SRF estimation across imaging techniques in literature in comparison to our results is provided in Table 4. Table 4 . Correlation coefficients for different renal function assessment methods. Imaging method 1 Imaging method 2 Correlation range (r) References Renal catheter DTPA 0.94 ( 31,32 ) DMSA DTPA 0.83–0.99 ( 33,34 ) [ 99m Tc]Tc-MAG3 DMSA 0.82–0.96 ( 35-38 ) [ 18 F]F-PSMA-1007 [ 99m Tc]Tc-MAG3 0.87 ( 19 ) [ 68 Ga]Ga-PSMA-11 [ 99m Tc]Tc-MAG3 0.91-0.96 ( 20,21 ) [ 68 Ga]Ga-PSMA-11 [ 99m Tc]Tc-MAG3 0.85 Present study [ 18 F]F-rhPSMA-7.3 [ 99m Tc]Tc-MAG3 0.88 Present study DTPA =diethylenetriaminepentaacetic acid, DMSA = 2,3 dimercaptosuccinic acid, MAG3 = mercapto-acetyltriglycine, 68 Ga = Gallium-68; PSMA = prostate-specific membrane antigen; 18 F = Fluorine-18, rh = radiohybrid. Besides its use in primary staging or restaging in biochemical recurrent disease, PSMA-PET/CT is frequently utilized to monitor response in patients with advanced, metastatic prostate cancer under systemic treatment involving nephrotoxic agents, such as PSMA-RLT ( 7-9 ). In addition to assessing global renal function through laboratory parameters, PSMA-PET/CT may provide side-separated renal function data as an inherent component of the imaging process, enabling clinicians to monitor changes in individual kidneys during treatment. Another possible application might be palliative external beam radiation therapy planning of retroperitoneal and/or lumbar spine lesions, where precise assessment of SRF is critical to minimize renal radiation exposure. By deriving SRF directly from PSMA-PET/CT, the need for additional imaging (such as [ 99m Tc]Tc-MAG3 scintigraphy) may be avoided, reducing procedural complexity for patients with advanced disease who often require optimized and streamlined care. In general, urinary tract obstruction is a relevant concern in patients with metastatic prostate cancer. Already at the time of initial diagnosis, hydronephrosis is present in approximately 23% of patients with newly diagnosed metastatic prostate cancer, and an additional 21% develop hydronephrosis during the course of their disease, as observed in a small retrospective cohort of 48 patients ( 39 ). Such cases often require interventions like ureteral stenting or nephrostomy prior to systemic therapy. In this context, diuretic renal scintigraphy remains the gold standard for evaluating urinary outflow: with modern 3D dynamic Cadmium-Zink-Tellurid Single-Photon Emission Computed Tomography (CZT SPECT/CT) imaging, it can achieve a sensitivity of 100% and a specificity of 93% in detecting acute ureteric obstruction, as shown by Ochoa-Figueroa et al. in a recent prospective study ( 40 ). Future research could explore the potential of dynamic PSMA-PET/CT to assess renal clearance and identify obstructive uropathies, similar to the capabilities of dynamic [ 99m Tc]Tc-MAG3 scintigraphy. Additionally, longitudinal studies at multiple time points, such as before therapy initiation and after each PSMA-RLT cycle, might provide valuable insights into renal function changes over time. These advancements could help establish PSMA-PET/CT as a more comprehensive tool for both functional and anatomical renal assessment. The main limitation of this study is the inherent patient cohort, as it consists of individuals with relatively preserved renal function who were eligible for PSMA-RLT. Patients with severe renal impairment are not candidates for PSMA-RLT and were therefore underrepresented in this study. While this may limit statistical accuracy at extreme SRF values, this does not diminish the clinical relevance, as the method is designed for application in a similar patient population where renal function is generally sufficient for PSMA-based treatments. CONCLUSION PSMA-PET/CT reliably assesses split renal function with strong agreement to [ 99m Tc]Tc-MAG3 scintigraphy, particularly with [ 18 F]F-flotufolastat showing slightly superior diagnostic accuracy. This may potentially eliminate the need for additional renal scintigraphy in the future and may simplify workflows and reduce patient burden. Future studies focusing on dynamic PET/CT and longitudinal renal monitoring could further enhance its utility, reinforcing its role as a comprehensive “one-stop-shop” imaging solution for patients with prostate cancer. Abbreviations PSMA Prostate-Specific Membrane Antigen PET Positron Emission Tomography CT Computed Tomography SRF Split Renal Function [ 99 mTc]Tc-MAG3 Technetium-99m Mercaptoacetyltriglycine [ 18 F]F-rhPSMA-7.3 Fluor-18 Flotufolastat (radiohybrid PSMA ligand) [ 68 Ga]Ga-PSMA-11 Gallium-68 PSMA-11 ROC Receiver Operating Characteristic ACI Accumulation Index eGFR estimated Glomerular Filtration Rate AUC Area Under the Curve RLT Radioligand Therapy LuPSMA Lutetium-177–labeled PSMA radioligand mCRPC metastatic Castration-Resistant Prostate Cancer TER Tubular Extraction Rate ROI Region of Interest SUVmax Maximum Standardized Uptake Value SUVmean Mean Standardized Uptake Value RPCS Renal Pelvic Caliceal System DMSA Dimercaptosuccinic Acid DTPA Diethylenetriaminepentaacetic Acid CZT Cadmium-Zinc-Telluride SPECT Single Photon Emission Computed Tomography R² Coefficient of Determination CI Confidence Interval Declarations Ethics approval and consent to participate All patients provided written informed consent for the clinical examination and reported investigations were conducted in accordance with the Declaration of Helsinki and with national regulations. The local ethics committee approved the retrospective analysis (permits: 2019-99_2-S-SR, updated on May 31, 2023). Consent for publication Not applicable Funding Not applicable Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests Isabel Rauscher and Matthias Eiber received consulting fees, research funding and travel support from Blue Earth Diagnostics Ltd. Outside the submitted work, Matthias Eiber reports fees from Novartis/AAA (consultant, speaker), Telix (consultant), Bayer (consultant, research funding), RayzeBio (consultant), Point Biopharma (consultant), Eckert-Ziegler (speaker), ABX GmbH (speaker), and Janssen Pharmaceuticals (consultant, speakers bureau); Parexel (image review) and Bioclinica (image review; and a patent application for rhPSMA. He and other inventors are entitled to royalties on sales of [ 18 F]F-flotufolastat. Wolfgang A Weber reports research support fees from Blue Earth Diagnostics Ltd, ITM, Novartis, and Pentixapharm. He has also acted as a consultant for these companies. There are no other conflicts of interest to disclose. Acknowledgements The authors thank the medical technicians and the staff of the radiochemistry group for their dedicated and reliable clinical work. Author contributions Michael Christian Marius Gammel drafted the manuscript. All authors read, revised and approved the final manuscript. Code availability Not applicable References Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71:209-249. Chodyla MK, Eiber M, Wetter A, Rauscher I. [Hybrid imaging in prostate cancer : Status quo and future applications]. Radiologe. 2020;60:386-393. Park SY, Zacharias C, Harrison C, et al. 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Eur J Nucl Med Mol Imaging. 2018;45:2218-2228. Bubeck B. Methoden zur quantitativen Clearancebestimmung. Der Nuklearmediziner. 2003;2003; 26(3): 169-180. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986;1:307-310. Giavarina D. Understanding Bland Altman analysis. Biochem Med (Zagreb). 2015;25:141-151. Piepsz A, Denis R, Ham HR, Dobbeleir A, Schulman C, Erbsmann F. A simple method for measuring separate glomerular filtration rate using a single injection of 99mTc-DTPA and the scintillation camera. J Pediatr. 1978;93:769-774. Chanard J, Ruiz JC, Liehn JC, et al. Assessment of divided renal function by renography. Validation in patients with separate urine collections from each kidney. Clin Nephrol. 1982;18:291-296. Miyazaki C, Harada H, Shuke N, Okizaki A, Miura M, Hirano T. (99m)Tc-DTPA dynamic SPECT and CT volumetry for measuring split renal function in live kidney donors. Ann Nucl Med. 2010;24:189-195. Momin MA, Abdullah MNA, Reza MS. Comparison of relative renal functions calculated with (99m)Tc-DTPA and (99m)Tc-DMSA for kidney patients of wide age ranges. Phys Med. 2018;45:99-105. Llamas-Elvira JM, Martinez-Paredes M, Jimenez-Heffernan A, et al. 99Tcm-MAG3 for quantitation of differential renal function. Nucl Med Commun. 1989;10:759-764. Bair HJ, Becker W, Schott G, Kuhn RH, Wolf F. Is there still a need for Tc-99m DMSA renal imaging? Clin Nucl Med. 1995;20:18-21. Ardela Diaz E, Miguel Martinez B, Gutierrez Duenas JM, Diez Pascual R, Garcia Arcal D, Dominguez Vallejo FJ. [Comparative study of differential renal function by DMSA and MAG-3 in congenital unilateral uropathies]. Cir Pediatr. 2002;15:118-121. Aktas GE, Inanir S. Relative renal function with MAG-3 and DMSA in children with unilateral hydronephrosis. Ann Nucl Med. 2010;24:691-695. Erbatu OM, T. Obstructive Uropathy in Advanced Prostate Cancer. Bull Urooncol. 2023;22(2):57-61. Ochoa-Figueroa M, Borbely K, Hasselqvist D, et al. 3D dynamic diuretic renal scintigraphy using a hybrid whole body CZT SPECT/CT camera protocol in the evaluation of acute ureteric obstruction caused by ureteric stone. EJNMMI Rep. 2024;8:27. Cite Share Download PDF Status: Published Journal Publication published 03 Feb, 2026 Read the published version in EJNMMI Research → Version 1 posted Editorial decision: Minor Revision 11 Jan, 2026 Reviewers agreed at journal 23 Sep, 2025 Reviewers invited by journal 19 Sep, 2025 Editor assigned by journal 18 Sep, 2025 First submitted to journal 17 Sep, 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. 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1","display":"","copyAsset":false,"role":"figure","size":1789801,"visible":true,"origin":"","legend":"\u003cp\u003eBland–Altman plots comparing PSMA-PET-derived SRF with [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3-based SRF, showing (A) agreement between [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastat\u003csup\u003e \u003c/sup\u003e-derived SRF and [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3-derived SRF, and (B) agreement between [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11-derived SRF and [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3-derived SRF.\u003c/p\u003e\n\u003cp\u003eSolid blue lines represent mean differences, while dashed brown lines indicate the limits of agreement (±\u0026nbsp;1.96 SD).\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e18\u003c/sup\u003eF\u0026nbsp;=\u0026nbsp;Fluorine-18; \u003csup\u003e68\u003c/sup\u003eGa\u0026nbsp;=\u0026nbsp;Gallium-68; MAG3\u0026nbsp;=\u0026nbsp;mercapto-acetyltriglycine; PET\u0026nbsp;=\u0026nbsp;positron emission tomography; SD\u0026nbsp;=\u0026nbsp;standard deviation; SRF\u0026nbsp;=\u0026nbsp;split renal function; ⁹⁹ᵐTc = Technetium-99m.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7528938/v1/18581cf2c821bb0c6959a97f.png"},{"id":92574838,"identity":"14b47be8-2ff7-4f80-ba54-edbd7dad9e9a","added_by":"auto","created_at":"2025-10-01 08:14:02","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2553039,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation between [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11-based SRF and [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3-derived SRF for the right kidney.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e68\u003c/sup\u003eGa\u0026nbsp;=\u0026nbsp;Gallium-68; MAG3\u0026nbsp;=\u0026nbsp;mercapto-acetyltriglycine; PET\u0026nbsp;=\u0026nbsp;positron emission tomography; SRF\u0026nbsp;=\u0026nbsp;split renal function; ⁹⁹ᵐTc = Technetium-99m.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7528938/v1/dfa20fbe8b87d0aa72506f4b.png"},{"id":92573047,"identity":"282cfd74-7048-4342-af8e-877ed1e75bd1","added_by":"auto","created_at":"2025-10-01 08:06:02","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":3091007,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation between [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastat-based SRF and [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3-derived SRF for the right kidney.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e18\u003c/sup\u003eF\u0026nbsp;=\u0026nbsp;Fluorine-18; MAG3\u0026nbsp;=\u0026nbsp;mercapto-acetyltriglycine; PET\u0026nbsp;=\u0026nbsp;positron emission tomography; SRF\u0026nbsp;=\u0026nbsp;split renal function; ⁹⁹ᵐTc = Technetium-99m.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-7528938/v1/e7fb00ee0f3caadaae4d928d.png"},{"id":92574839,"identity":"66335554-c737-42a9-a0af-c1ccc308d82a","added_by":"auto","created_at":"2025-10-01 08:14:02","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":4728370,"visible":true,"origin":"","legend":"\u003cp\u003eROC curves for (A) [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastat\u003csup\u003e \u003c/sup\u003ePSMA-PET-derived SRF in identifying [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3-SRF \u0026lt; 25%; (B) [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastat-derived SRF in identifying [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3-SRF \u0026lt; 40%; (C) [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11-derived SRF in identifying [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3-SRF \u0026lt; 25%; and (D) [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11-PSMA-PET-derived SRF in identifying [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3-SRF \u0026lt; 40%.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e18\u003c/sup\u003eF\u0026nbsp;=\u0026nbsp;Fluorine-18; \u003csup\u003e68\u003c/sup\u003eGa\u0026nbsp;=\u0026nbsp;Gallium-68; AUC = area under the ROC curve; MAG3\u0026nbsp;=\u0026nbsp;mercapto-acetyltriglycine; PET\u0026nbsp;=\u0026nbsp;positron emission tomography; PSMA = prostate-specific membrane antigen; ROC = receiver operating characteristic; SRF\u0026nbsp;=\u0026nbsp;split renal function; ⁹⁹ᵐTc = Technetium-99m.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-7528938/v1/43f81a0cae84d9ef599030fa.png"},{"id":102233992,"identity":"4abcd824-d001-4fca-9674-899cfe959785","added_by":"auto","created_at":"2026-02-09 16:02:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":19380581,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7528938/v1/57765d69-a6e2-4e42-a882-254cd0216d34.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003e\u003cstrong\u003eSplit Renal Function Estimation Using [\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e18\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003eF]F-Flotufolastat PET/CT: Comparison with [\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e68\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003eGa]Ga-PSMA-11 and [\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e99m\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003eTc]Tc-MAG3 Scintigraphy\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eProstate cancer is one of the most common malignancies in men (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e), requiring precise diagnostic and therapeutic approaches, particularly in advanced stages. Prostate-specific membrane antigen (PSMA) has emerged as a critical target in prostate cancer management due to its overexpression in malignant prostate tissue (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Imaging with [\u003csup\u003e68\u003c/sup\u003eGa]- or [\u003csup\u003e18\u003c/sup\u003eF]-labeled PSMA-targeted radiopharmaceuticals plays a pivotal role in staging, restaging, and monitoring response to therapy (\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7 CR8\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Additionally, PSMA-targeted radioligand therapy (RLT) with [\u003csup\u003e177\u003c/sup\u003eLu]Lutetium-labeled PSMA (LuPSMA) radioligands has become an essential life-prolonging treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC) (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eDespite its specificity for prostate cancer cells, PSMA is also physiologically expressed in the proximal tubule cells of the kidneys (\u003cspan additionalcitationids=\"CR12 CR13 CR14\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). This renal uptake introduces a potential risk of radiation nephrotoxicity during PSMA-RLT (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). However, its presence also provides an opportunity to evaluate renal function non-invasively using PSMA-PET. The assessment of renal function is critical for prostate patients prior to therapeutic interventions (e.g. external beam radiation therapy, LuPSMA RLT) to minimize toxicity and optimize treatment planning (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eUntil now, dynamic renal scintigraphy using Technetium-99m [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-mercapto-acetyltriglycine ([\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3) remains the clinical standard for assessing global and split renal function (SRF) and excluding urinary outflow obstruction. [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3 scintigraphy accurately estimates tubular renal function but requires an additional imaging procedure, which can be time-consuming and burdensome, particularly for patients with painful skeletal metastases.\u003c/p\u003e\u003cp\u003ePrevious preliminary studies have demonstrated a strong correlation between PSMA-PET-derived SRF and [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3-based SRF using [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11 and [\u003csup\u003e18\u003c/sup\u003eF]F-PSMA-1007 (\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). However, these studies have been limited by relatively small patient populations (n\u0026thinsp;=\u0026thinsp;28\u0026ndash;97). \u003csup\u003e18\u003c/sup\u003eF- Flotufolastat ([\u003csup\u003e18\u003c/sup\u003eF]F-rhPSMA-7.3), is a recently FDA-approved radiohybrid PSMA-PET radiopharmaceutical for staging and restaging of prostate cancer (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) but has not yet been investigated in assessing renal function.\u003c/p\u003e\u003cp\u003eIn this study, we retrospectively evaluated a large cohort of patients with mCRPC who underwent both PSMA-PET and [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3 scintigraphy. We aimed to compare the accuracy of SRF derived using [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11 and [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastat versus the standard [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3 scintigraphy. Additionally, we investigated correlations between absolute renal uptake derived from PSMA-PET, tubular excretion rate (TER) of [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3, and serum creatinine levels to explore global renal function parameters.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003ePatient Characteristics\u003c/h2\u003e\u003cp\u003eThis retrospective study included 302 patients with advanced mCRPC who underwent either [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11 PET/CT (n\u0026thinsp;=\u0026thinsp;81) or [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastat (n\u0026thinsp;=\u0026thinsp;221) and [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3 scintigraphy as part of their clinical evaluation for PSMA RLT at the, Technical University of Munich University Hospital, Germany. All patients provided written informed consent for the clinical examination and reported investigations were conducted in accordance with the Declaration of Helsinki and with national regulations. The local ethics committee approved the retrospective analysis (permits: 2019-99_2-S-SR, updated on May 31, 2023). All patients evaluated for RLT between October 2014 and October 2022 were included, with a median interval of 15 days between PSMA-PET and [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3 scintigraphy. Patient characteristics are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\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\u003ePatient characteristics\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAll patients (N\u0026thinsp;=\u0026thinsp;302)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePatients who underwent [\u003c/b\u003e\u003csup\u003e\u003cb\u003e68\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eGa]Ga-PSMA-11 PET/CT, n\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e81\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePatients who underwent [\u003c/b\u003e\u003csup\u003e\u003cb\u003e18\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eF]F-flotufolastat PET/CT, n\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e221\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge, years\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e72\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInjected activity [\u003c/b\u003e\u003csup\u003e\u003cb\u003e18\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eF]F-flotufolastat, MBq\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e288\u0026thinsp;\u0026plusmn;\u0026thinsp;60\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInjected activity [\u003c/b\u003e\u003csup\u003e\u003cb\u003e68\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eGa]Ga-PSMA-11, MBq\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e122\u0026thinsp;\u0026plusmn;\u0026thinsp;36\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAcquisition p.i. [\u003c/b\u003e\u003csup\u003e\u003cb\u003e18\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eF], minutes\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e72\u0026thinsp;\u0026plusmn;\u0026thinsp;13\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAcquisition p.i. [\u003c/b\u003e\u003csup\u003e\u003cb\u003e68\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eGa], minutes\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e56\u0026thinsp;\u0026plusmn;\u0026thinsp;12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTER, mL/min\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e201\u0026thinsp;\u0026plusmn;\u0026thinsp;46\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCreatinine, mg/dL\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.29\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eeGFR, mL/min/1.73 m\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e77\u0026thinsp;\u0026plusmn;\u0026thinsp;19\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePatients with eGFR\u0026thinsp;\u0026gt;\u0026thinsp;60 ml/min, n\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e228\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePatients with eGFR\u0026thinsp;\u0026le;\u0026thinsp;60 ml/min, n\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e74\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSplit function, %\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e50\u0026thinsp;\u0026plusmn;\u0026thinsp;12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePSA\u003c/b\u003e\u003csub\u003e\u003cb\u003emean\u003c/b\u003e\u003c/sub\u003e, \u003cb\u003eng/mL\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e338\u0026thinsp;\u0026plusmn;\u0026thinsp;700\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003eUnless otherwise stated, all values are mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003e\u003csup\u003e68\u003c/sup\u003eGa = Gallium-68; PSMA\u0026thinsp;=\u0026thinsp;prostate-specific membrane antigen; PET\u0026thinsp;=\u0026thinsp;positron emission tomography; CT\u0026thinsp;=\u0026thinsp;computed tomography; \u003csup\u003e18\u003c/sup\u003eF = Fluorine-18; rh\u0026thinsp;=\u0026thinsp;radiohybrid; MBq\u0026thinsp;=\u0026thinsp;megabecquerel; TER\u0026thinsp;=\u0026thinsp;tubular excretion rate; eGFR\u0026thinsp;=\u0026thinsp;estimated glomerular filtration rate, PSA\u0026thinsp;=\u0026thinsp;prostate-specific antigen.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cp\u003e\u003cstrong\u003e[\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastat\u003csup\u003e\u0026nbsp;\u003c/sup\u003ePET/CT and [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11\u0026nbsp;PET/CT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe radiolabeling of both [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastat\u003csup\u003e\u0026nbsp;\u003c/sup\u003e and [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11 followed established protocols described in previous studies (\u003cem\u003e24\u003c/em\u003e)(\u003cem\u003e25\u003c/em\u003e).\u003c/p\u003e\n\u003cp\u003eFor [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastat, an intravenous bolus of 288 \u0026plusmn; 60 MBq was administered, and PET scanning commenced approximately 72 \u0026plusmn; 13 minutes post injection. For [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11, a mean activity of 122 \u0026plusmn; 36 MBq was injected intravenously, with PET scanning commencing at a mean of 56 \u0026plusmn; 12 minutes post-injection. All patients received a diluted oral contrast medium (300 mg Telebrix, Guerbet) and a diagnostic CT scan in the portal venous phase, performed 80 seconds after intravenous administration of iodinated contrast (Imeron 300, Bracco Imaging). PET/CT scans for both [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastat and [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11were conducted using either a Siemens Biograph mCT Flow or Siemens Biograph Vision 600 scanner (Siemens Healthineers. Imaging was performed in 3D mode, with acquisition speeds of 0.8 mm/s (Biograph mCT Flow) and 1.1 mm/s (Biograph Vision 600) for [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastat, and 1.1\u0026ndash;1.5 mm/second or 3\u0026ndash;4 minutes per bed position for [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11.\u003c/p\u003e\n\u003cp\u003eReconstruction was carried out using ordered-subset expectation maximization (TrueX, 4 iterations, 8 subsets) for both radiopharmaceuticals. A Gaussian smoothing filter of 2 mm (full width at half maximum) was applied for [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastat, and 5 mm (full width half maximum) for [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11. Emission data were corrected for randoms, dead time, scatter, and attenuation for both protocols, ensuring consistent and accurate quantitative analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSRF from PSMA-PET\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSRF was calculated using PET data based on renal uptake of regions of interest (ROI) were delineated using 50% isocontour thresholds to extract both maximum standardized uptake value (SUV\u003csub\u003emax\u003c/sub\u003e) and mean standardized uptake value (SUV\u003csub\u003emean\u003c/sub\u003e). For PET, ROIs were manually drawn over the kidneys, excluding the renal pelvic caliceal system (RPCS). On CT, the renal parenchyma was defined while excluding the renal pelvic caliceal system and cystic structures.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe SRF was calculated using the following formula:\u003c/p\u003e\n\u003cp\u003e\u003cimg width=\"366\" height=\"44\" src=\"data:image/png;base64,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\" alt=\"image\"\u003e\u003c/p\u003e\n\u003cp\u003eCalculations were performed separately using SUV\u003csub\u003emax\u003c/sub\u003e and SUV\u003csub\u003emean\u003c/sub\u003e, with volumes derived from either PET (functional) or CT (anatomical) data. All ROI placements and analyses were reviewed by an experienced nuclear medicine physician (I.R.) to ensure consistency and accuracy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCalculation and Statistical Evaluation of the PET-Based Accumulation Index (ACI)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo explore potential associations between PSMA-PET-derived measures and global renal function, an Accumulation Index (ACI) was calculated for each patient by dividing the combined renal parenchymal volume (segmented from CT) by the sum of the SUV\u003csub\u003emean\u003c/sub\u003e estimates from both kidneys. This approach was inspired by the methodology proposed by Weissinger et al. for somatostatin receptor targeted PET/CT imaging, where the ACI showed strong positive correlation with MAG3-derived renal function parameters (\u003cem\u003e26\u003c/em\u003e). Although PSMA tracers differ substantially in their pharmacokinetics, particularly regarding proximal tubular binding, we considered this concept worth exploring in our cohort. Due to non-normal distribution of ACI and estimated glomerular filtration rate (eGFR) (Shapiro\u0026ndash;Wilk test, p \u0026lt; 0.0001 for both), correlations were assessed using Spearman\u0026rsquo;s rank correlation coefficient (\u0026rho;). Analyses were performed separately for [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastat and [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e[\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3-Scintigraphy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo ensure optimal hydration, all patients were instructed to drink at least 10 mL of mineral water per kilogram of bodyweight 30 minutes prior to scintigraphy. Dynamic renal scintigraphy with [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3 was performed per European Association of Nuclear Medicine guidelines (\u003cem\u003e27\u003c/em\u003e) and the Bubeck method (\u003cem\u003e28\u003c/em\u003e), using approximately 100 MBq of [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3 and planar dynamic imaging with both posterior and anterior detectors for 20 minutes. Current CT images were used to determine whether calculation of the geometric mean was required. ROI were drawn manually over the renal parenchyma, including the renal pelvic caliceal system, as well as the aorta and background regions. In cases of inadequate[\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3 excretion observed in post-micturition images, furosemide was administered, followed by an additional 20 minutes of imaging. SRF was calculated from renal activity curves between 60\u0026ndash;100 seconds. Tubular extraction rate (TER) was determined using the two-sample plasma clearance method, and side-separated TER was calculated by multiplying SRF with the total TER.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll statistical analyses were performed using Microsoft Excel and MedCalc version 23.1.3 (MedCalc Software Ltd, Ostend, Belgium). Continuous variables were expressed as mean \u0026plusmn; standard deviation. Normality was assessed using the Shapiro\u0026ndash;Wilk test. The Pearson correlation coefficient (r) was calculated to evaluate the linear relationship between PSMA-PET-derived SRF(PET-SRF) and [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3-derived SRF ([\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3-SRF) as the reference standard. In addition, correlations between PET-based measures of absolute renal uptake and TER were assessed to evaluate global renal function. Bland\u0026ndash;Altman analysis (\u003cem\u003e29,30\u003c/em\u003e) was conducted to assess agreement between methods, including the calculation of mean differences, limits of agreement, and the proportion of values within a predefined range of \u0026plusmn; 10 %. Linear regression analysis was performed to model the relationship between PET-SRF and [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3-SRF, with coefficients of determination (R\u003csup\u003e2\u003c/sup\u003e), regression equations, and residual analyses reported. Normality of residuals was tested using the D\u0026apos;Agostino\u0026ndash;Pearson test.\u003c/p\u003e\n\u003cp\u003eReceiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic accuracy of PET-SRF for identifying severely impaired renal function ([\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3-SRF \u0026le; 25 %) and reduced renal function ([\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3-SRF \u0026le; 40 %). The area under the ROC curve (AUC), sensitivity, specificity, and optimal thresholds based on the Youden Index were reported. Statistical significance was set at p\u0026lt;0.05.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eRenal function parameters were within an overall preserved range, with a mean serum creatinine of 1.0 ± 0.29 mg/dL and mean eGFR of 77 ± 19 mL/min/1.73 m². A total of 228 (75%) patients presented with an eGFR above 60 mL/min. Mean TER was 201 ± 46 mL/min. Mean SRF based on [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3 was 50 ± 12%.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSRF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCorrelation Between PET- and\u0026nbsp;\u003c/em\u003e[\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3\u003cem\u003e-Derived SRF\u0026nbsp;\u003c/em\u003eA strong linear relationship was observed across all tested PET SRF combinations (SUV\u003csub\u003emax\u003c/sub\u003e and SUV\u003csub\u003emean\u003c/sub\u003e, volumes derived from PET or CT) and [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3-SRF, with Pearson correlation coefficients (r) ranging from 0.835 to 0.881 (all p\u0026lt;0.0001). The best agreement was achieved using SUV\u003csub\u003emean\u003c/sub\u003e in combination with CT-based renal volumes (r = 0.881), therefore all subsequent analyses were performed using this approach. Table 2 summarizes the findings of the ¹⁸F-flotufolastat analysis.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e2\u003c/strong\u003e. Methods for SRF calculation using \u0026sup1;⁸F-flotufolastat\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"605\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 434px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMethods for SRF-calculation using \u0026sup1;⁸F-flotufolastat\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePearson \u003cem\u003er\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 434px;\"\u003e\n \u003cp\u003e[\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3\u003cstrong\u003e-SRF \u0026amp; SRF(SUV\u003csub\u003emean\u003c/sub\u003e, CT-Volume)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e0.881\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt; 0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 434px;\"\u003e\n \u003cp\u003e[\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3\u003cstrong\u003e-SRF \u0026amp; SRF(SUV\u003csub\u003emax\u003c/sub\u003e, CT-Volume)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e0.878\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt; 0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 434px;\"\u003e\n \u003cp\u003e[\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3\u003cstrong\u003e-SRF \u0026amp; SRF(SUV\u003csub\u003emax\u003c/sub\u003e, PET-Volume)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e0.849\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt; 0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 434px;\"\u003e\n \u003cp\u003e[\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3\u003cstrong\u003e-SRF \u0026amp; SRF(SUV\u003csub\u003emean\u003c/sub\u003e, PET-Volume)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e0.835\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt; 0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eSRF = split renal function; \u003csup\u003e18\u003c/sup\u003eF = Fluorine-18; rh = radiohybrid; PSMA = prostate-specific membrane antigen; MAG3\u0026nbsp;= mercapto-acetyltriglycine, SUV\u003csub\u003emean\u003c/sub\u003e = mean standardized uptake value; CT = computed tomography; SUV\u003csub\u003emax\u003c/sub\u003e = maximum standardized uptake value; PET = positron emission tomography; ⁹⁹ᵐTc = Technetium-99m.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;Agreement Between PET- and\u0026nbsp;\u003c/em\u003e[\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3\u003cem\u003e-SRF Estimates\u003c/em\u003eBland–Altman analysis revealed no significant systematic bias for either radiopharmaceutical. For [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11, the mean difference between PET-SRF and [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3-SRF was -1.18% (\u003cem\u003ep\u003c/em\u003e = 0.15), with limits of agreement ranging from -15.30 % to 12.95 %. Additionally, 83% of values were within ± 10% of agreement. For [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastat, the mean difference was slightly smaller at -0.56% (p=0.15), with narrower limits of agreement (-11.88% to +10.75%) and a higher proportion of values (92%) falling within ±\u0026nbsp;10%. (Figure 1)\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;Modeling the Relationship Between PET- and\u0026nbsp;\u003c/em\u003e[\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3\u003cem\u003e-SRF\u0026nbsp;\u003c/em\u003eThe relationship between PET-SRF and [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3-SRF was modeled using linear regression. For [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11, the linear regression model produced an R\u003csup\u003e2\u003c/sup\u003e-value of 0.703, with the equation y\u0026nbsp;=\u0026nbsp;−0.1513\u0026nbsp;+\u0026nbsp;1.2763x (Figure 2). The slope (β1\u0026nbsp;=\u0026nbsp;1.2763) significantly deviated from 1 (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.0001), suggesting a slight overestimation of higher SRF values by PET.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBy comparison, [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastat showed a stronger fit, with an R\u003csup\u003e2\u003c/sup\u003e-value of 0.7738 and the regression equation y\u0026nbsp;=\u0026nbsp;0.1536\u0026nbsp;+\u0026nbsp;0.7020x (Figure 3). The slope (β1\u0026nbsp;=\u0026nbsp;0.7020) also significantly deviated from 1 (p\u0026lt;0.0001), indicating a slight underestimation. However, residuals for [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastat were not normally distributed (p\u0026lt;0.0001, D’Agostino–Pearson test), potentially limiting the model's validity for extreme values. An overview of both regression models is provided in Table 3.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e3\u003c/strong\u003e. Linear regression models for estimating\u0026nbsp;[\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3-SRF from PET-SRF values\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"586\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRadioligand\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eR\u0026sup2;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRegression equation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSlope (\u0026beta;₁) \u0026ne; 1 (p)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntercept (\u0026beta;₀)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eResiduals normally distributed (p)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e⁶⁸Ga-PSMA-11\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003e0.703\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003e\u003cem\u003ey\u003c/em\u003e = \u0026minus;0.1513 + 1.2763x\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e\u0026lt; 0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026minus;0.1513\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003eyes (\u003cem\u003ep\u003c/em\u003e \u0026gt; 0.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026sup1;⁸F-flotufolastat\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003e0.774\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003e\u003cem\u003ey\u003c/em\u003e = 0.1536 + 0.7020x\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e\u0026lt; 0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e0.1536\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003eno (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.0001)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eMAG3 = mercapto-acetyltriglycine; SRF = split renal function; PET = positron emission tomography; R\u003csup\u003e2\u003c/sup\u003e = coefficient of determination; \u003csup\u003e68\u003c/sup\u003eGa = Gallium-68; PSMA = prostate-specific membrane antigen; \u003csup\u003e18\u003c/sup\u003eF = Fluorine-18; ⁹⁹ᵐTc = Technetium-99m.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;Diagnostic Accuracy of PET-SRF to Detect Functional Impairment\u0026nbsp;\u003c/em\u003eThe ROC analysis confirmed the excellent diagnostic performance of both [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11 and [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastatin distinguishing impaired split renal function at thresholds of [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3-SRF ≤ 25% and ≤ 40%.\u003c/p\u003e\n\u003cp\u003eAt the 25 % threshold, [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11 achieved an AUC of 0.942 (95 % CI: 0.866–0.982; p\u0026lt;0.0001), with a sensitivity of 84% and a specificity of 100%. [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastat demonstrated a slightly superior performance with an AUC of 0.997 (95 % CI: 0.978–1.000; p\u0026lt;0.0001), achieving a sensitivity of 98% and a specificity of 100%.\u003c/p\u003e\n\u003cp\u003eAt the 40% threshold, [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11 showed an AUC of 0.979 (95 % CI: 0.920–0.998; p\u0026lt;0.0001), with a sensitivity of 89% and a specificity of 100%. Similarly, [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastatachieved an AUC of 0.954 (95 % CI: 0.917–0.978; p\u0026lt;0.0001), with a sensitivity of 90% and a specificity of 90%. (Figure 4)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssessment of Global Renal Function Using the PET-Based ACI\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe ACI showed a non-normal distribution with pronounced right skew and kurtosis (Shapiro–Wilk \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.0001). The mean eGFR in the overall cohort was 77 ± 19 mL/min/1.73 m². For patients who underwent [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastatPET/CT (n=212), no significant correlation was observed between ACI and eGFR (Spearman’s ρ = 0.056 [p=0.414]). Similarly, in the [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11 subgroup (n=79), no significant association was found (Spearman’s ρ = –0.071 [\u003cem\u003ep\u003c/em\u003e = 0.536]).\u0026nbsp;\u003c/p\u003e\n\n\n\n\n\n\n"},{"header":"DISCUSSION","content":"\u003cp\u003eRenal function is a critical factor for many prostate cancer therapies, including [\u003csup\u003e177\u003c/sup\u003eLu]Lu-PSMA therapy, and PSMA-PET/CT offers the potential advantage of calculating SRF as part of every routine scan. Previous studies have explored various radiopharmaceuticals in small cohorts as proof-of-concept investigations (n = 28–97) (\u003cem\u003e19-21\u003c/em\u003e). To the best of our knowledge, this is the first study to directly compare [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastatwith [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11 against [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3 renal scintigraphy, and to do so in a large patient cohort. This study demonstrated a strong correlation (see Table 2) between PSMA-PET-derived SRF and [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3-based SRF for both radiopharmaceuticals, with [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastatexhibiting a slightly superior diagnostic performance due to its narrower limits of agreement and higher sensitivity.\u003c/p\u003e\u003cp\u003eThe strong correlations with [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3 observed in this study (r = 0.85 for [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11 and r = 0.88 for [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastat) are in line with prior PSMA PET studies, which reported correlation coefficients between r = 0.85 and r = 0.96 for SRF estimation compared to MAG3 scintigraphy. For example, Rosar et al. found r = 0.91 for [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11, Gabela et al. reported r = 0.96 for the same tracer, and Rassek et al. demonstrated r = 0.87 for [\u003csup\u003e18\u003c/sup\u003eF]F-PSMA-1007 (\u003cem\u003e31-34\u003c/em\u003e). Notably, [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-DMSA scintigraphy achieves similar correlation coefficients for SRF when compared to MAG3 or DTPA-based methods, typically in the range of r = 0.82–0.99 (\u003cem\u003e35-38\u003c/em\u003e). A compact overview of SRF estimation across imaging techniques in literature in comparison to our results is provided in Table 4.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e Correlation coefficients for different renal function assessment methods.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eImaging method 1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eImaging method 2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCorrelation range (r)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eReferences\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRenal catheter\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eDTPA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e0.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(\u003cem\u003e31,32\u003c/em\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDMSA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eDTPA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e0.83\u0026ndash;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(\u003cem\u003e33,34\u003c/em\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e[\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eDMSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e0.82\u0026ndash;0.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(\u003cem\u003e35-38\u003c/em\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e[\u003csup\u003e18\u003c/sup\u003eF]F-PSMA-1007\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e[\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(\u003cem\u003e19\u003c/em\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e[\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e[\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e0.91-0.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(\u003cem\u003e20,21\u003c/em\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e[\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e[\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003ePresent study\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e[\u003csup\u003e18\u003c/sup\u003eF]F-rhPSMA-7.3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e[\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003ePresent study\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eDTPA =diethylenetriaminepentaacetic acid, DMSA = 2,3 dimercaptosuccinic acid, MAG3 = mercapto-acetyltriglycine, \u003csup\u003e68\u003c/sup\u003eGa = Gallium-68; PSMA = prostate-specific membrane antigen; \u003csup\u003e18\u003c/sup\u003eF = Fluorine-18, rh = radiohybrid.\u003c/p\u003e\u003cp\u003eBesides its use in primary staging or restaging in biochemical recurrent disease, PSMA-PET/CT is frequently utilized to monitor response in patients with advanced, metastatic prostate cancer under systemic treatment involving nephrotoxic agents, such as PSMA-RLT (\u003cem\u003e7-9\u003c/em\u003e). In addition to assessing global renal function through laboratory parameters, PSMA-PET/CT may provide side-separated renal function data as an inherent component of the imaging process, enabling clinicians to monitor changes in individual kidneys during treatment.\u003c/p\u003e\u003cp\u003eAnother possible application might be palliative external beam radiation therapy planning of retroperitoneal and/or lumbar spine lesions, where precise assessment of SRF is critical to minimize renal radiation exposure. By deriving SRF directly from PSMA-PET/CT, the need for additional imaging (such as [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3 scintigraphy) may be avoided, reducing procedural complexity for patients with advanced disease who often require optimized and streamlined care.\u003c/p\u003e\u003cp\u003eIn general, urinary tract obstruction is a relevant concern in patients with metastatic prostate cancer. Already at the time of initial diagnosis, hydronephrosis is present in approximately 23% of patients with newly diagnosed metastatic prostate cancer, and an additional 21% develop hydronephrosis during the course of their disease, as observed in a small retrospective cohort of 48 patients (\u003cem\u003e39\u003c/em\u003e).\u0026nbsp;Such cases often require interventions like ureteral stenting or nephrostomy prior to systemic therapy. In this context, diuretic renal scintigraphy remains the gold standard for evaluating urinary outflow: with modern 3D dynamic Cadmium-Zink-Tellurid Single-Photon Emission Computed Tomography (CZT SPECT/CT) imaging, it can achieve a sensitivity of 100% and a specificity of 93% in detecting acute ureteric obstruction, as shown by Ochoa-Figueroa et al. in a recent prospective study\u0026nbsp;(\u003cem\u003e40\u003c/em\u003e). Future research could explore the potential of dynamic PSMA-PET/CT to assess renal clearance and identify obstructive uropathies, similar to the capabilities of dynamic [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3 scintigraphy. Additionally, longitudinal studies at multiple time points, such as before therapy initiation and after each PSMA-RLT cycle, might provide valuable insights into renal function changes over time. These advancements could help establish PSMA-PET/CT as a more comprehensive tool for both functional and anatomical renal assessment.\u003c/p\u003e\u003cp\u003eThe main limitation of this study is the inherent patient cohort, as it consists of individuals with relatively preserved renal function who were eligible for PSMA-RLT. Patients with severe renal impairment are not candidates for PSMA-RLT and were therefore underrepresented in this study. While this may limit statistical accuracy at extreme SRF values, this does not diminish the clinical relevance, as the method is designed for application in a similar patient population where renal function is generally sufficient for PSMA-based treatments.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003ePSMA-PET/CT reliably assesses split renal function with strong agreement to [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3 scintigraphy, particularly with [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastat showing slightly superior diagnostic accuracy. This may potentially eliminate the need for additional renal scintigraphy in the future and may simplify workflows and reduce patient burden. Future studies focusing on dynamic PET/CT and longitudinal renal monitoring could further enhance its utility, reinforcing its role as a comprehensive \u0026ldquo;one-stop-shop\u0026rdquo; imaging solution for patients with prostate cancer.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"0\" cellspacing=\"3\" cellpadding=\"0\" width=\"633\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003ePSMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 470px;\"\u003e\n \u003cp\u003eProstate-Specific Membrane Antigen\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003ePET\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 470px;\"\u003e\n \u003cp\u003ePositron Emission Tomography\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003eCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 470px;\"\u003e\n \u003cp\u003eComputed Tomography\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003eSRF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 470px;\"\u003e\n \u003cp\u003eSplit Renal Function\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003e[\u003csup\u003e99\u003c/sup\u003emTc]Tc-MAG3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 470px;\"\u003e\n \u003cp\u003eTechnetium-99m Mercaptoacetyltriglycine\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003e[\u003csup\u003e18\u003c/sup\u003eF]F-rhPSMA-7.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 470px;\"\u003e\n \u003cp\u003eFluor-18 Flotufolastat (radiohybrid PSMA ligand)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003e[\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 470px;\"\u003e\n \u003cp\u003eGallium-68 PSMA-11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003eROC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 470px;\"\u003e\n \u003cp\u003eReceiver Operating Characteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003eACI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 470px;\"\u003e\n \u003cp\u003eAccumulation Index\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003eeGFR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 470px;\"\u003e\n \u003cp\u003eestimated Glomerular Filtration Rate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003eAUC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 470px;\"\u003e\n \u003cp\u003eArea Under the Curve\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003eRLT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 470px;\"\u003e\n \u003cp\u003eRadioligand Therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003eLuPSMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 470px;\"\u003e\n \u003cp\u003eLutetium-177\u0026ndash;labeled PSMA radioligand\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003emCRPC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 470px;\"\u003e\n \u003cp\u003emetastatic Castration-Resistant Prostate Cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003eTER\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 470px;\"\u003e\n \u003cp\u003eTubular Extraction Rate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003eROI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 470px;\"\u003e\n \u003cp\u003eRegion of Interest\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003eSUVmax\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 470px;\"\u003e\n \u003cp\u003eMaximum Standardized Uptake Value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003eSUVmean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 470px;\"\u003e\n \u003cp\u003eMean Standardized Uptake Value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003eRPCS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 470px;\"\u003e\n \u003cp\u003eRenal Pelvic Caliceal System\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003eDMSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 470px;\"\u003e\n \u003cp\u003eDimercaptosuccinic Acid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003eDTPA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 470px;\"\u003e\n \u003cp\u003eDiethylenetriaminepentaacetic Acid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003eCZT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 470px;\"\u003e\n \u003cp\u003eCadmium-Zinc-Telluride\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003eSPECT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 470px;\"\u003e\n \u003cp\u003eSingle Photon Emission Computed Tomography\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003eR\u0026sup2;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 470px;\"\u003e\n \u003cp\u003eCoefficient of Determination\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003eCI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 470px;\"\u003e\n \u003cp\u003eConfidence Interval\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patients provided written informed consent for the clinical examination and reported investigations were conducted in accordance with the Declaration of Helsinki and with national regulations. The local ethics committee approved the retrospective analysis (permits: 2019-99_2-S-SR, updated on May 31, 2023).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIsabel Rauscher and Matthias Eiber received consulting fees, research funding and travel support from Blue Earth Diagnostics Ltd.\u003c/p\u003e\n\u003cp\u003eOutside the submitted work, Matthias Eiber reports fees from Novartis/AAA (consultant, speaker), Telix (consultant), Bayer (consultant, research funding), RayzeBio (consultant), Point Biopharma (consultant), Eckert-Ziegler (speaker), ABX GmbH (speaker), and Janssen Pharmaceuticals (consultant, speakers bureau); Parexel (image review) and Bioclinica (image review; and a patent application for rhPSMA. He and other inventors are entitled to royalties on sales of [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastat.\u003c/p\u003e\n\u003cp\u003eWolfgang A Weber reports research support fees from Blue Earth Diagnostics Ltd, ITM, Novartis, and Pentixapharm. He has also acted as a consultant for these companies.\u003c/p\u003e\n\u003cp\u003eThere are no other conflicts of interest to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the medical technicians and the staff of the radiochemistry group for their dedicated and reliable clinical work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMichael Christian Marius Gammel drafted the manuscript. All authors read, revised and\u003c/p\u003e\n\u003cp\u003eapproved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCode availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. \u003cem\u003eCA Cancer J Clin. \u003c/em\u003e2021;71:209-249.\u003c/li\u003e\n \u003cli\u003e Chodyla MK, Eiber M, Wetter A, Rauscher I. [Hybrid imaging in prostate cancer : Status quo and future applications]. \u003cem\u003eRadiologe. \u003c/em\u003e2020;60:386-393.\u003c/li\u003e\n \u003cli\u003e Park SY, Zacharias C, Harrison C, et al. 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A Comparison of (68)Ga-PSMA PET/CT-Based Split Renal Function with (99m)Tc-MAG3 Renography in Patients with Metastatic Castration-Resistant Prostate Carcinoma Treated with (177)Lu-PSMA. \u003cem\u003eDiagnostics (Basel). \u003c/em\u003e2024;14.\u003c/li\u003e\n \u003cli\u003e Rosar F, Pauly P, Ries M, et al. Determination of split renal function by PSMA imaging: comparison of (68)Ga-PSMA-11 PET with (99m)Tc-MAG3 scintigraphy. \u003cem\u003eAm J Nucl Med Mol Imaging. \u003c/em\u003e2020;10:249-256.\u003c/li\u003e\n \u003cli\u003e Kroenke M, Mirzoyan L, Horn T, et al. Matched-Pair Comparison of (68)Ga-PSMA-11 and (18)F-rhPSMA-7 PET/CT in Patients with Primary and Biochemical Recurrence of Prostate Cancer: Frequency of Non-Tumor-Related Uptake and Tumor Positivity. \u003cem\u003eJ Nucl Med. \u003c/em\u003e2021;62:1082-1088.\u003c/li\u003e\n \u003cli\u003e Rauscher I, Karimzadeh A, Schiller K, et al. Detection efficacy of (18)F-rhPSMA-7.3 PET/CT and impact on patient management in patients with biochemical recurrence of prostate cancer after radical prostatectomy and prior to potential salvage treatment. \u003cem\u003eJ Nucl Med. \u003c/em\u003e2021;62:1719-1726.\u003c/li\u003e\n \u003cli\u003e Wurzer A, Di Carlo D, Schmidt A, et al. Radiohybrid Ligands: A Novel Tracer Concept Exemplified by (18)F- or (68)Ga-Labeled rhPSMA Inhibitors. \u003cem\u003eJ Nucl Med. \u003c/em\u003e2020;61:735-742.\u003c/li\u003e\n \u003cli\u003e Eder M, Neels O, Muller M, et al. Novel Preclinical and Radiopharmaceutical Aspects of [68Ga]Ga-PSMA-HBED-CC: A New PET Tracer for Imaging of Prostate Cancer. \u003cem\u003ePharmaceuticals (Basel). \u003c/em\u003e2014;7:779-796.\u003c/li\u003e\n \u003cli\u003e Weissinger M, Seyfried KC, Ursprung S, et al. 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A simple method for measuring separate glomerular filtration rate using a single injection of 99mTc-DTPA and the scintillation camera. \u003cem\u003eJ Pediatr. \u003c/em\u003e1978;93:769-774.\u003c/li\u003e\n \u003cli\u003e Chanard J, Ruiz JC, Liehn JC, et al. Assessment of divided renal function by renography. Validation in patients with separate urine collections from each kidney. \u003cem\u003eClin Nephrol. \u003c/em\u003e1982;18:291-296.\u003c/li\u003e\n \u003cli\u003e Miyazaki C, Harada H, Shuke N, Okizaki A, Miura M, Hirano T. (99m)Tc-DTPA dynamic SPECT and CT volumetry for measuring split renal function in live kidney donors. \u003cem\u003eAnn Nucl Med. \u003c/em\u003e2010;24:189-195.\u003c/li\u003e\n \u003cli\u003e Momin MA, Abdullah MNA, Reza MS. Comparison of relative renal functions calculated with (99m)Tc-DTPA and (99m)Tc-DMSA for kidney patients of wide age ranges. \u003cem\u003ePhys Med. \u003c/em\u003e2018;45:99-105.\u003c/li\u003e\n \u003cli\u003e Llamas-Elvira JM, Martinez-Paredes M, Jimenez-Heffernan A, et al. 99Tcm-MAG3 for quantitation of differential renal function. \u003cem\u003eNucl Med Commun. \u003c/em\u003e1989;10:759-764.\u003c/li\u003e\n \u003cli\u003e Bair HJ, Becker W, Schott G, Kuhn RH, Wolf F. Is there still a need for Tc-99m DMSA renal imaging? \u003cem\u003eClin Nucl Med. \u003c/em\u003e1995;20:18-21.\u003c/li\u003e\n \u003cli\u003e Ardela Diaz E, Miguel Martinez B, Gutierrez Duenas JM, Diez Pascual R, Garcia Arcal D, Dominguez Vallejo FJ. [Comparative study of differential renal function by DMSA and MAG-3 in congenital unilateral uropathies]. \u003cem\u003eCir Pediatr. \u003c/em\u003e2002;15:118-121.\u003c/li\u003e\n \u003cli\u003e Aktas GE, Inanir S. Relative renal function with MAG-3 and DMSA in children with unilateral hydronephrosis. \u003cem\u003eAnn Nucl Med. \u003c/em\u003e2010;24:691-695.\u003c/li\u003e\n \u003cli\u003e Erbatu OM, T. Obstructive Uropathy in Advanced Prostate Cancer. \u003cem\u003eBull Urooncol.\u003c/em\u003e2023;22(2):57-61.\u003c/li\u003e\n \u003cli\u003e Ochoa-Figueroa M, Borbely K, Hasselqvist D, et al. 3D dynamic diuretic renal scintigraphy using a hybrid whole body CZT SPECT/CT camera protocol in the evaluation of acute ureteric obstruction caused by ureteric stone. \u003cem\u003eEJNMMI Rep. \u003c/em\u003e2024;8:27.\u003c/li\u003e\n\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":false,"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":"Split renal function, PSMA, [99mTc]Tc-MAG3, prostate cancer, PET/CT","lastPublishedDoi":"10.21203/rs.3.rs-7528938/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7528938/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Physiological prostate-specific membrane antigen (PSMA) expression in renal proximal tubules results in radiopharmaceutical uptake in PSMA-PET, suggesting the potential to assess renal function. Thus, we evaluated whether PSMA-PET/CT allowed estimation of split renal function (SRF), potentially replacing [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3 scintigraphy. We retrospectively analyzed 302 patients with metastatic castration-resistant prostate cancer undergoing PSMA-PET/CT using either [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastat ([\u003csup\u003e18\u003c/sup\u003eF]F-rhPSMA-7.3) (n=221) or [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11 (n=81), along with [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3 scintigraphy, prior to PSMA radioligand therapy. SRF was calculated from PSMA-PET/CT using mean standardized uptake values and CT-derived renal volumes. SRF was calculated from [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3 using standard integral analysis. Correlations between PET-derived SRF (PET-SRF) and [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3 -derived SRF ([\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3-SRF) were assessed using Pearson correlation and Bland–Altman analysis. Receiver operating characteristic (ROC) analyses were conducted to evaluate diagnostic performance in detecting impaired renal function (SRF ≤\u0026nbsp;25% and ≤40%). A PET-based accumulation index (ACI) was explored for correlation with estimated glomerular filtration rate (eGFR).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Strong correlations were found between PET-SRF and [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3-SRF (r=0.88 for [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastat, r=0.85 for [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11; both p\u0026lt;0.0001). Bland–Altman analysis showed a smaller mean bias and narrower limits of agreement for [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastat\u003csup\u003e \u003c/sup\u003e(-0.56%; -11.88% to +10.75%) compared with [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11 (-1.18%; -15.3% to +12.95%), with 92% versus 83% of values within ±\u0026nbsp;10%, respectively. ROC analysis confirmed excellent accuracy for identifying [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3-SRF ≤\u0026nbsp;25% (area under the curve [AUC] = 0.997 for [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastat; AUC = 0.942 for [\u003csup\u003e68\u003c/sup\u003eGa]Ga-PSMA-11). ACI and eGFR were not significantly correlated (Spearman’s ρ=0.048; p=0.49]).\u003cstrong\u003e Conclusion:\u003c/strong\u003e PSMA-PET/CT provides reliable estimates of SRF, with [\u003csup\u003e18\u003c/sup\u003eF]F-flotufolastat\u003csup\u003e \u003c/sup\u003eshowing slightly superior agreement with [\u003csup\u003e99m\u003c/sup\u003eTc]Tc-MAG3 scintigraphy. This may potentially eliminate the need for additional renal scintigraphy for SRF assessment in the future and may simplify workflows and reduce patient burden.\u003c/p\u003e","manuscriptTitle":"Split Renal Function Estimation Using [18F]F-Flotufolastat PET/CT: Comparison with [68Ga]Ga-PSMA-11 and [99mTc]Tc-MAG3 Scintigraphy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-01 08:05:57","doi":"10.21203/rs.3.rs-7528938/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor Revision","date":"2026-01-11T12:16:33+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-09-23T09:07:20+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-19T11:29:14+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-18T07:04:17+00:00","index":"","fulltext":""},{"type":"submitted","content":"EJNMMI Research","date":"2025-09-17T14:54:39+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":"0e9a1e5d-68f8-4034-a912-d4c40ed022dd","owner":[],"postedDate":"October 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-09T16:00:31+00:00","versionOfRecord":{"articleIdentity":"rs-7528938","link":"https://doi.org/10.1186/s13550-026-01385-0","journal":{"identity":"ejnmmi-research","isVorOnly":false,"title":"EJNMMI Research"},"publishedOn":"2026-02-03 15:57:12","publishedOnDateReadable":"February 3rd, 2026"},"versionCreatedAt":"2025-10-01 08:05:57","video":"","vorDoi":"10.1186/s13550-026-01385-0","vorDoiUrl":"https://doi.org/10.1186/s13550-026-01385-0","workflowStages":[]},"version":"v1","identity":"rs-7528938","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7528938","identity":"rs-7528938","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}