18F-PSMA-1007 PET/MR for Early Detection of Biochemical Recurrence of Prostate Cancer in Very Low (≤ 0.5 ng/mL) Prostate-Specific Antigen Levels

18F-PSMA-1007 PET/MR for Early Detection of Biochemical Recurrence of Prostate Cancer in Very Low (≤ 0.5 ng/mL) Prostate-Specific Antigen Levels | 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 18F-PSMA-1007 PET/MR for Early Detection of Biochemical Recurrence of Prostate Cancer in Very Low (≤ 0.5 ng/mL) Prostate-Specific Antigen Levels Ko-Han Lin, Tzu-Chun Wei, Shu-Huei Shen, William Ji-Shien Huang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4571324/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose To evaluate the diagnostic efficacy of 18 F-PSMA-1007 PET/MR (PSMA-PET) in detecting biochemical recurrence (BCR) of prostate cancer (PCa) at very low (≤ 0.5 ng/mL) prostate-specific antigen (PSA) levels. Methods We recruited 157 PCa patients with BCR post-radical prostatectomy or radiation therapy between May 2021 and January 2023. Among them, 52 patients with PSA ≤ 0.5 ng/mL underwent PSMA-PET imaging. The imaging protocol included multiparametric MRI (mpMRI) and PET data analysis, with lesion classification based on PSMA-RADS version 1.0. Results The PSMA-PET imaging demonstrated a 63.5% detection rate for recurrent PCa in patients with low PSA levels. PSMA-PET detected 34 local recurrent lesions, 12 metastatic lymph nodes, and 4 skeletal metastases. Follow-up imaging reclassified initially equivocal lesions, increasing the detection rate to 73.1%. Outcomes from PSMA-PET imaging significantly influenced personalized treatment strategies, impacting clinical decisions for 17% of the participants in our investigation. Conclusion PSMA-PET significantly enhances the detection of recurrent PCa at low PSA levels, providing precise localization and aiding in personalized treatment strategies. Further research is essential to optimize its clinical application and validate long-term efficacy. prostate cancer PSA biochemical recurrence 18F-PSMA-1007 PET/MR Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Prostate cancer (PCa) remains a significant health concern for men globally, ranking as the second most commonly diagnosed cancer and the fifth leading cause of cancer-related deaths among men. In 2020, there were approximately 1,414,000 new cases and 375,304 deaths attributed to prostate cancer, underscoring its substantial impact on men's health worldwide and highlighting the ongoing need for effective diagnostic and therapeutic strategies to manage and reduce the burden of this disease (Sung et al., 2021 ; Wang et al., 2022 ). Despite advancements in early detection and treatment, managing PCa, particularly in its recurrence and/or metastases, continues to pose significant challenges. Recurrence and metastasis often require more complex and aggressive treatment approaches, emphasizing the critical need for continued research and development of advanced diagnostic tools and therapeutic methods to improve patient outcomes and manage the disease more effectively. The issue of PCa recurrence after primary treatment stands as a major concern, with biochemical recurrence (BCR) affecting 20–50% of patients (Cornford et al., 2021 ; Mottet et al., 2021 ). This underscores the importance of a nuanced approach to detection and management for improving patient outcomes. The American Urological Association and European Association of Urology have established guidelines for recognizing BCR, highlighting the role of prostate-specific antigen (PSA) levels in diagnosis (Simon et al., 2022 ). Typically, recurrence is indicated by a rise in PSA levels, defined as PSA reaching or exceeding 0.2 ng/mL post-prostatectomy or increasing by 2 ng/mL above the nadir after radiation therapy (Cookson et al., 2007 ; Cornford et al., 2021 ). Managing patients with PCa who experience BCR following primary treatment is complex due to the challenge of balancing the prevention of clinical progression with the risk of over-treatment. Adjuvant therapy is reserved for at-risk patients, while recommendations for salvage therapy vary and lack definitive evidence. An individualized, multidisciplinary approach is essential, with advances in imaging techniques potentially improving future management (Artibani et al., 2018 ). In this context, molecular imaging techniques, particularly PET/CT scans using 18 F-Fluciclovine and prostate-specific membrane antigen (PSMA) radiotracers, have revolutionized the detection and management of recurrent PCa (Eiber et al., 2017 ; Savir-Baruch & Schuster, 2022 ). 18 F-Fluciclovine, an amino acid analogue, has shown promise in identifying recurrent disease by localizing to prostate cancer cells via amino acid transporters (Marcus et al., 2020 ). This modality has proven especially beneficial in patients with low serum PSA levels (≤ 1 ng/mL), offering a new avenue for early detection and facilitating targeted salvage therapy (Andriole et al., 2019 ). Clinical trials, such as the FALCON study, have highlighted its potential in improving PSA response compared to traditional methods (Scarsbrook et al., 2020 ). On the other hand, PSMA PET/CT imaging agent like 68 Ga-PSMA-11 and 18 F-PSMA-1007, provides a high sensitivity and specificity for detecting both local and distant recurrences (Cornford et al., 2021 ; Giesel, Kesch, et al., 2017 ; Mottet et al., 2021 ; Perera et al., 2016 ). These radiotracers have shown advantages over 18 F-Fluciclovine in certain aspects, particularly in detecting disease with minimal urinary bladder activity (Calais et al., 2019 ; Pernthaler et al., 2019 ), which is crucial for accurate localization. A meta-analysis comparing these modalities revealed pooled detection rates favoring PSMA PET/CT, especially in patients with very low PSA levels (< 0.5 ng/mL) (Tan et al., 2020 ), suggesting its superior efficacy in early and precise disease localization. The continuous development of PET imaging technologies, including the introduction of simultaneous PET/MR scanners, represents a significant advancement in the diagnostic arsenal against PCa. PET/MR, combining the detailed anatomical imaging of MRI with the functional insights of PET, has demonstrated superiority in assessing local recurrence and lymph node involvement. This technology, particularly when combined with PSMA ligands, offers a comprehensive evaluation of recurrent disease, enhancing the potential for early intervention and personalized treatment strategies. However, the struggle against recurrent PCa is increasingly being enhanced by revolutionary developments in diagnostic imaging technologies. Ongoing research and clinical trials are critical for identifying the best ways to use these technologies, moving clinicians closer to providing more effective, personalized care for patients with recurrent PCa. Consequently, our study is dedicated to evaluating the diagnostic efficacy of 18 F-PSMA-1007 PET/MR (PSMA-PET) in detecting early BCR at notably low PSA levels (≤ 0.5 ng/mL), aiming to refine treatment approaches and improve patient outcomes. Materials and methods Patient recruitment This prospective study was conducted at a medical center in northern Taiwan, focusing on patients with histologically confirmed PCa and BCR following radical prostatectomy or radiation therapy. BCR was defined as a PSA level greater than 0.1 ng/mL measured more than six weeks after prostatectomy, or a PSA increase of more than 2 ng/mL above the nadir following external beam radiation therapy (EBRT) (Roach et al., 2006 ; Shore et al., 2023 ). All participants had undergone radical prostatectomy as a curative treatment. The study protocol was reviewed and approved by the Institutional Review Board of the study hospital (IRB #2021-02-008BC). 18 F-PSMA-1007 PET/MRI protocol Participants were instructed to fast for at least 6 hours prior to undergoing the imaging procedures. The protocol began with an intravenous administration of the 18 F-PSMA-1007. The dosage was calculated based on the participant's body weight, at 4 MBq/kg, followed by simultaneous PET/MRI (SIGNA PET/MR, GE Healthcare, Waukesha, Wisconsin, USA) imaging covering the body from the thighs to the skull, commencing 90 minutes after the injection. This system uniquely combines 3T MR imaging capabilities with PET imaging, employing state-of-the-art silicon photomultipliers (SiPM) for enhanced photodetection. The PET data acquired were reconstructed into dynamic multi-frame images using a sophisticated three-dimensional time-of-flight (TOF)-enabled ordered subsets expectation maximization (OSEM) iterative algorithm. This process included the incorporation of a point-spread function kernel, which significantly improves the resolution of the images. Multiparametric MRI (mpMRI) was began with axial T1-weighted images for a basic anatomy overview, followed by axial, sagittal, and coronal T2-weighted images for precise mapping of the prostate and surrounding areas. Axial diffusion-weighted imaging (DWI) with an apparent diffusion coefficient (ADC) map was used to identify potential cancer areas by detecting restricted diffusion. The study also included dynamic contrast-enhanced (DCE) MRI scans with a gadolinium-based contrast agent to examine the prostate's vascular patterns and enhance lesion visibility, capturing 30 dynamic phases. Furthermore, it expanded to whole-body MRI assessments, using DWI and 3D T1-weighted axial scans before and after contrast, to detect metastatic disease and provide a comprehensive view, highlighting the protocol's thorough approach in evaluating prostate cancer. The integrated PET and T1-weighted axial scan images were acquired for a thorough evaluation of prostate cancer, addressing both local tumor characteristics and potential disease spread. By combining PET with various MRI techniques, the aim was to offer a detailed, comprehensive view of the tumor, essential for formulating an effective treatment plan. Image analysis and strategies of patient management The image analysis of the PET and mpMRI images in this study was conducted through a meticulous and collaborative approach. Initially, the mpMRI scans were subject to an independent review by a radiologist, tasked with the identification and staging of any tumors within the prostate. This crucial step laid the groundwork for further analysis. Following this initial examination, a collaborative assessment was undertaken, synthesizing of both a radiologist and a nuclear medicine physician. Lesions were classified under PSMA-RADS version 1.0 (Rowe et al., 2018 ) ; categories 4 (high focal PSMA uptake at locations characteristic of prostate cancer without corresponding lesions on MR) and 5 (high focal PSMA uptake coincident with a definitive anatomic lesion on MR) were interpreted as positive findings. Subsequent treatment protocols were developed by the multidisciplinary team (MDT) specializing in PCa. Patients identified with these positive lesions underwent treatment with local EBRT plus short-term androgen deprivation therapy (ADT) for 26 individuals, local EBRT alone for 5 individuals, or ADT alone for 2 individuals. For those presenting with equivocal (PSMA-RADS 3A or 3B) or negative findings, a minimum follow-up period of 12 months (ranging between 14 to 30 months) was implemented, alongside imaging assessments (via PSMA-PET or mpMRI) to monitor any progression or changes. Nevertheless, not all participants underwent histopathological verification of their results. Results Patient Demographics and PSA Characteristics From May 2021 to January 2023, 157 patients with histology-proven PCa and BCR after radical prostatectomy or radiation therapy were recruited for this study. Among these patients, the results of 54 patients whose PSA ≤ 0.5 ng/mL (mean: 0.34 ± 0.1 ng/mL; range 0.11–0.50 ng/mL) were retrospectively reviewed and analyzed. Two patients, despite with positive findings, were excluded from the analysis because the result still inclusive after one and a half-year follow-up. Finally, 52 patients were enrolled in this study. The pathologic stagings were pT2N0M0 (n = 16), T3aN0M0 (n = 24), pT3N0M0 (n = 11), and pT3aN1M0 (n = 1). PSMA-PET Detection Rate and Comparison with mpMRI The PSMA-PET imaging demonstrated a high detection rate in patients with low PSA levels. Out of the 52 patients, 33 were confirmed positive by PSMA-PET, resulting in a detection rate of 63.5%. This substantial detection rate is particularly noteworthy given the low PSA levels (≤ 0.5 ng/mL) in the cohort, highlighting the sensitivity of PSMA-PET for early detection of recurrent PCa. Simultaneous mpMRI yielded negative findings in nine of these 33 PSMA-PET positive patients. This discrepancy suggests that PSMA-PET may detect lesions that mpMRI fails to identify, emphasizing the enhanced sensitivity of PSMA-PET imaging (Fig. 1 ). Comparative analysis revealed that patients with positive PSMA-PET results had significantly higher PSA levels (0.36 ± 0.10 ng/mL) compared to those with negative findings (0.30 ± 0.11 ng/mL) (p = 0.014) (Table 1 ). However, no statistically significant correlation was observed between PSA doubling-time (PSAdt) and PSMA-PET results (p = 0.32), indicating that PSAdt does not significantly impact the detection capability of PSMA-PET in this patient population. (D)-(F) An 81-year-old patient with PCa underwent a PSMA-PET study due to a gradual increase in PSA (0.23 ng/mL; PSAdt: 13.8 months). (D) Axial fused PSMA PET/MRI revealed a lesion with moderately increased PSMA uptake (SUVmax 3.27) in the posterior urinary bladder wall (red arrow). However, simultaneous (E) T2WI-MRI and (F) the fusion image of DWI with T2WI-MRI only showed vague signals (red dashed circles). Table 1 Gleason Scores and PSA Doubling Time in Patients with Positive and Negative PSMA-PET Results PSMA-PET (+), n = 33 PSMA-PET (-), n = 19 GS 7 7 6 PSAdt ≤ 6 months 13 10 PSAdt > 6 months 20 9 Mean PSA (range) 0.36 ± 0.10 (0.19–0.5)* 0.30 ± 0.11 (0.11–0.48) Mean PSAdt (range) 9.59 ± 6.44 (2.9–27.0) 9.05 ± 6.38 (1.9–21.4) GS = Gleason Scores, PSA = prostate-specific antigen, PSAdt = PSA Doubling Time, PSMA-PET = 18 F-PSMA-1007 PET/MR. *p = 0.009 Further analysis of the patients with positive and negative PSMA-PET results, showed a distinct distribution of Gleason scores (GS) and PSAdt (Table 1 ). Among the PSMA-PET positive group, 26 patients had a GS of 7, while 7 had a GS > 7. The mean PSAdt was slightly higher in the PSMA-PET positive group (9.59 ± 6.44 months) compared to the negative group (9.05 ± 6.38 months). Local Recurrence and Metastatic Findings PSMA-PET imaging identified 34 local recurrent lesions in 31 patients, accounting for 59.6% of the cohort. The majority of these lesions (56%) were located at anastomotic sites. The reduced urinary activity associated with 18 F-PSMA-1007 facilitated the clear detection of seven lesions near the urinary bladder wall, which constituted 20% of the findings. Additionally, one lesion adjacent to the posterior urinary bladder wall was accurately identified as a recurrence in the vas deferens. PSMA-PET imaging detected 12 metastatic lymph nodes in 10 patients, representing 24% of all detected lesions. All metastatic lymph nodes were confined to the pelvic cavity, with no extra-pelvic detections. The short-axis diameter of these lymph nodes ranged from 2 to 8 mm. Notably, one lymph node categorized under PSMA-RADS category 5 had a short-axis diameter of 8 mm and a maximum standardized uptake value (SUVmax) of 16.69. Furthermore, six patients with nodal metastases were concurrently identified with local recurrences. Four skeletal metastases were detected in four patients, representing 8% of all detected lesions. These metastases were located within the pelvis and included two lesions classified as PSMA-RADS category 5, one as category 4, and one as category 3 (Table 2 ). Table 2 Detection of Lesions and SUVmax in Various Recurrence Sites Recurrence Site No. of detected lesions (No. of patients) Mean SUVmax ± SD (Range) Local recurrence 34 (31) 6.25 ± 3.72 (2.5–17.04) Anastomosis 19 6.51 ± 3.97 (2.5–17.04) Urinary bladder wall 7 6.83 ± 4.26 (3.01–14.24) Seminal vesicle 5 5.03 ± 2.80 (2.63–9.66) Vas deferans 1 4.16 Perirectal space 1 3.01 Pelvic floor 1 8.52 Pelvic lymph nodes 12 (10) 7.80 ± 6.62 (2.35–22.01) Bone metastasis 4 (4) 3.51 ± 1.46 (1.5–5.13) SUVmax = maximum standardized uptake value, SD = standard deviation. Longitudinal Follow-Up and Reclassification The longitudinal follow-up and reclassification of initially equivocal lesions (PSMA-RADS score 3) underscored the dynamic nature of recurrent prostate cancer and the importance of continuous monitoring. During the retrospective analysis, initially equivocal lesions were found to be positive in five patients upon follow-up scans conducted 14–26 months later. This reclassification increased the detection rate from 63.5–73.1%, demonstrating the importance of longitudinal monitoring in patients with indeterminate initial findings. Table 3 details the characteristics of these reclassified lesions, including their locations, PSA levels, PSAdt, and SUVmax values. For instance, one patient (#1) initially had an equivocal lesion at the anastomosis with a PSA of 0.26 ng/mL and a PSAdt of 1.9 months. Upon re-evaluation 26 months later, this lesion was confirmed as positive with a SUVmax of 2.5. Similarly, patient #2 had an equivocal lesion near the urinary bladder wall with a PSA of 0.23 ng/mL and a PSAdt of 2.4 months, which was later confirmed as positive through mpMRI with a SUVmax of 3.82 after 12 months. Table 3 Reclassification of Initially Equivocal (Category 3) Lesions as True-positive on Follow-up Patient No. Location PSA PSAdt SUVmax Modality Interval #1 Anastomosis 0.26 1.9 2.5 PSMA-PET 26 m #2 Urinary bladder wall 0.23 2.4 3.82 mpMRI 12 m #3 Right external iliac node 0.46 3.3 2.35 PSMA-PET 14 m #4 Right internal iliac node 0.23 4.6 2.8 PSMA-PET 15 m #5 Sacrum 0.4 19 m 2.61 PSMA-PET 26 m PSA = prostate-specific antigen, PSAdt = PSA Doubling Time, SUVmax = maximum standardized uptake value, PSMA-PET = 18 F-PSMA-1007 PET/MR, mpMRI = multiparametric MRI, m = month. The reclassification of initially equivocal lesions as true positives upon follow-up also validates the need for ongoing research and development of more sensitive imaging technologies. These findings suggest that PSMA-PET imaging can significantly improve patient outcomes by enabling earlier detection and intervention, ultimately reducing the burden of recurrent prostate cancer. Statistical Analysis and Correlations In-depth statistical analysis was performed to understand the relationships between various clinical parameters and the efficacy of PSMA-PET imaging. No significant correlation was found between PSAdt and the detection rate of PSMA-PET (p = 0.32), suggesting that the rate of PSA increase is not a determining factor for the sensitivity of PSMA-PET in detecting recurrent lesions at low PSA levels. Furthermore, the analysis showed no significant correlations between PSA level-SUVmax and PSAdt-SUVmax of the detected lesions (p = 0.85 and 0.20, respectively). This indicates that the SUVmax, which measures the intensity of radiotracer uptake, is not influenced by PSA kinetics, reaffirming the robustness of PSMA-PET imaging irrespective of PSA dynamics (Table 4 ). Table 4 Comparison of Clinical Characteristics Between Patients with Positive and Negative PSMA-PET Results PSMA-PET (+) PSMA-PET (-) Patients’ No 38 14 GS 7 10 3 PSAdt ≤ 6 months 17 5 PSAdt > 6 months 21 9 Mean PSA (range) 0.36 ± 0.10 (0.19–0.5)* 0.29 ± 0.09 (0.11–0.48) Mean PSAdt (range) 9.15 ± 6.54 (1.9–27.0) 10.06 ± 6.02 (4.5–21.4) GS = Gleason Scores, PSA = prostate-specific antigen, PSAdt = PSA Doubling Time, PSMA-PET = 18 F-PSMA-1007 PET/MR. *p = 0.014 Discussion Our research demonstrates a remarkable detection rate of up to 63.5% for PSMA-PET in patients with PSA levels below 0.5 ng/mL. This high detection rate underscores the significant diagnostic value of PSMA-PET imaging in identifying recurrent PCa even at very low PSA levels. Upon retrospective investigation of these cases two years post the initial PSMA-PET scans, we found that initially equivocal lesions (PSMA-RADS score 3) were confirmed positive in five patients, raising the detection rate to 73.1%. This highlights the sustained efficacy of this imaging modality in detecting disease recurrence over time and emphasizes the necessity of follow-up imaging in cases with initially indeterminate results. Moreover, outcomes from PSMA-PET imaging significantly influence personalized treatment strategies, impacting clinical decisions for 17% of the participants in our investigation. The findings from our study carry several important clinical implications. Firstly, the detection of very small lesions with mild uptake initially categorized as equivocal highlights the challenges inherent in PSMA-PET imaging at low PSA levels. For instance, one patient (Table 3 , patient #1) had very small lesions with slight elevation in uptake, making definitive categorization difficult. Follow-up PSMA-PET scans after two years showed a significant rise in tracer uptake, confirming their pathological nature (Fig. 2 ). This underscores the importance of expertise in interpreting PSMA-PET scans and the potential benefits of repeated imaging to capture the dynamic nature of PCa recurrence. In another case (Table 3 , patient #2), high urine activity hindered the accurate interpretation of the initial scan. A distinct lesion identified in a subsequent MRI study became visible upon review of the initial PSMA-PET scan, which had been obscured by urine activity. This emphasizes the critical role of complementary imaging modalities and the necessity for radiologists to be vigilant about potential artifacts that may obscure true-positive findings in PSMA-PET scans. Moreover, the confirmation of very small lymph nodes and skeletal metastases upon follow-up imaging demonstrates the importance of meticulous image analysis. Two patients (Table 3 , patient #3, #4) had small lymph nodes that initially raised suspicion but were not definitively identified as pathological. Follow-up PSMA-PET scans conducted two years later confirmed these as lymph node metastases (Fig. 3 ). Similarly, small sacral lesions detected initially were later confirmed as metastatic in follow-up scans (Table 3 , patient #5) (Fig. 4 ). These cases highlight the need for follow-up imaging to confirm and validate initial suspicions, especially for small and difficult-to-interpret lesions. Previous literature data indicate that the detection rates for PSA levels below 0.5 ng/mL are approximately 38–45% for 68 Ga-PSMA-11 (Fendler et al., 2019 ; Kuppermann et al., 2022 ). The unique hepatobiliary excretion pathway of 18 F-PSMA-1007, in contrast to the renal excretion observed with 68 Ga-PSMA-11, results in clearer imaging of the pelvic region (Allach et al., 2022 ; Giesel, Hadaschik, et al., 2017 ). This reduced interference is critical for identifying local recurrences near the bladder and urethra, areas where conventional imaging techniques often face challenges due to tracer accumulation in the urine. Furthermore, the integration of PET and MR imaging technologies enhances overall diagnostic precision (Mayerhoefer et al., 2020 ; Pichler et al., 2008 ). MR imaging is renowned for its exceptional soft tissue contrast, which, when combined with the functional imaging capabilities of PET, enables a more comprehensive evaluation of pelvic lesions (Ebrahimi et al., 2024 ). Consequently, PSMA-PET offers a more precise visualization of the pelvic region, facilitating well-informed clinical decisions. Our study also highlights the advantages of 18 F-PSMA-1007 over other radiotracers, such as 68 Ga-PSMA-11, particularly in patients with low PSA levels. The unique hepatobiliary excretion pathway of 18 F-PSMA-1007 reduces interference from urinary activity, facilitating clearer imaging of the pelvic region and improving the detection of local recurrences near the bladder and urethra. This characteristic is crucial for accurate localization of recurrent disease and supports the integration of PSMA-PET into routine clinical practice for managing BCR of PCa. The superior imaging quality provided by 18 F-PSMA-1007 enables more precise interventions and potentially improves patient outcomes by allowing for more accurate treatment planning (Awenat et al., 2021 ). When comparing 18 F-PSMA-1007 with other 18 F-labeled PSMA tracers such as 18 F-DCFPyL and 18 F-rhPSMA-7, it is important to consider their respective strengths and limitations. 18 F-PSMA-1007 offers the advantage of minimal renal excretion, which reduces urinary bladder activity and thus improves pelvic imaging clarity. However, 18 F-DCFPyL, which is predominantly excreted through the kidneys, may have higher sensitivity in detecting lesions in areas less affected by urinary activity but can be more challenging for pelvic imaging due to higher urinary excretion. Additionally, 18 F-DCFPyL has shown effectiveness in detecting liver metastases, making it particularly useful in scenarios where liver involvement is suspected (Giesel et al., 2018 ). Similarly, 18 F-rhPSMA-7 combines the benefits of both renal and hepatobiliary excretion, which can be advantageous for detecting lesions across various regions but may still present challenges in pelvic imaging similar to those of 18 F-DCFPyL. The renal clearance can lead to higher urinary activity, which may obscure lesions near the bladder and ureters, but hepatobiliary excretion can mitigate some of these issues by reducing urinary interference, improving image quality in other regions (Wurzer et al., 2020 ). In addition, 18 F-DCFPyL has been noted for its high tumor uptake and favorable biodistribution, making it a strong candidate for whole-body imaging (Morris et al., 2021 ; Pienta et al., 2021 ; Song et al., 2022 ; Wurzer et al., 2020 ). Each tracer thus has unique benefits, with 18 F-PSMA-1007 being highly effective for detailed pelvic imaging, 18 F-DCFPyL for its overall sensitivity and whole-body imaging capabilities, and 18 F-rhPSMA-7 for its balanced excretion properties (Song et al., 2022 ). Nevertheless, 18 F-PSMA-1007's minimal renal excretion makes it particularly advantageous for pelvic imaging by minimizing urinary interference, thereby enhancing the clarity and accuracy of detecting local recurrences. The absence of significant correlations between these variables highlights the complexity of PCa recurrence and the multifactorial nature of its detection. This indicates that PSMA-PET imaging may be influenced by various biological and technical factors that require an integrated approach for accurate assessment. The multifactorial nature of PCa recurrence necessitates comprehensive diagnostic strategies that encompass clinical, biochemical, and advanced imaging data. These integrated approaches are essential for providing a thorough assessment of recurrent disease and tailoring individualized treatment plans. The findings from our statistical analysis reinforce the reliability of PSMA-PET imaging as an independent diagnostic tool that can effectively detect recurrent PCa across a spectrum of PSA dynamics. This independence from PSA kinetics underscores the robustness of PSMA-PET imaging and its utility in a diverse range of clinical scenarios. Furthermore, the lack of correlation with PSA kinetics suggests that PSMA-PET could be particularly useful in cases where PSA levels alone do not provide a clear picture of disease status, thereby enhancing the overall diagnostic process. Moreover, the significant impact of PSMA-PET imaging on personalized treatment strategies is evident from our findings (Yan et al., 2024 ). The detection of recurrent disease at low PSA levels allows for timely and targeted interventions, such as local EBRT and ADT, which can significantly improve patient outcomes (Harsini et al., 2023 ; Yan et al., 2024 ). The treatment based on precise localization and characterization of recurrent lesions underscores the value of PSMA-PET imaging in the clinical management of PCa. By enabling early detection and accurate staging, PSMA-PET imaging facilitates the development of personalized treatment plans that are tailored to the specific needs and conditions of each patient, thereby enhancing the effectiveness of therapeutic interventions (Adnan & Basu, 2023; Gillette et al., 2023 ). Additionally, this approach minimizes unnecessary treatments and reduces potential side effects by focusing on targeted therapy, thereby improving the quality of life for patients. The precision of PSMA-PET imaging also supports ongoing monitoring and timely adjustments to treatment plans, which is crucial for managing recurrent PCa effectively. Both PSMA PET/MR and PSMA PET/CT have their unique advantages and limitations. PET/CT is widely available and typically faster, providing both metabolic and anatomic information which is crucial for initial staging and restaging of prostate cancer. The CT component, however, exposes patients to ionizing radiation and offers limited soft tissue contrast, which can be a limitation in certain clinical scenarios (Awenat et al., 2021 ). On the other hand, PET/MR offers superior soft tissue contrast due to the MRI component, which can be particularly advantageous in assessing local recurrences and pelvic lesions (Glemser et al., 2022 ; Mojsak et al., 2023 ). Additionally, MRI does not involve ionizing radiation, making it a safer option for repeated imaging, especially in younger patients or those requiring frequent follow-up scans. However, PET/MR is less available, more expensive, and generally takes longer than PET/CT, which may limit its use in some clinical settings. The choice between PET/CT and PET/MR should be based on the specific clinical scenario, patient characteristics, and the available resources, with PET/MR being preferable for detailed soft tissue evaluation and PET/CT for its accessibility and speed. Despite the promising results, our study has several limitations that should be noted. First, the sample size was relatively small, with only 52 patients included in the final analysis. This limited number may affect the generalizability of our findings to a broader population of patients of PCa with BCR. Second, our study was conducted at a single medical center in northern Taiwan, which may introduce selection bias and limit the applicability of the results to other settings or populations with different demographic or clinical characteristics. Third, not all participants underwent histopathological verification of their PSMA-PET or mpMRI results. This lack of confirmatory pathology could lead to potential misclassification of lesions and affect the accuracy of our findings. Fourth, while PSMA-PET demonstrated a high detection rate, the impact of false-positive results cannot be entirely ruled out, particularly in the context of very low PSA levels where non-specific uptake might occur. Finally, the retrospective nature of the follow-up for initially equivocal lesions could introduce bias and affect the interpretation of the dynamic changes observed in these lesions. Further prospective studies with larger cohorts and multi-center involvement are warranted to validate our findings and refine the clinical utility of PSMA-PET imaging in the management of recurrent PCa. Conclusion Our study revealed that, the use of PSMA-PET significantly enhances the detection of recurrent PCa at low PSA levels (≤ 0.5 ng/mL), providing precise localized anatomical and functional insights that enhance clinical decision-making. The integration of this advanced imaging modality into clinical practice has the potential to significantly improve patient outcomes through early detection and personalized treatment approaches. Further research and longitudinal studies are essential to optimize its application and validate its long-term efficacy in managing BCR of PCa. The continued evolution of PSMA-PET imaging techniques and their integration with other diagnostic modalities will likely play a pivotal role in advancing the management of recurrent PCa, ultimately leading to better patient care and improved survival rates. Declarations Author contributions All authors contributed to the study conception and design. Image acquisition, interpreting, and data analysis were performed by Ko-Han Lin, Tzu-Chun Wei, and Shu-Huei Shen. The first draft of the manuscript was written by Ko-Han Lin and Yuh-Feng Wang. William Ji-Shien Huang and Nan-Jing Peng supervised the writing of the manuscript. Revision and final version of the manuscript were written by Yuh-Feng Wang. All authors read and approved the final manuscript. Funding This research was supported by the grant of Taipei Veterans General Hospital (V111E-008-1). Ethical approval This study was approved by the Institutional Review Board of the Taipei Veterans General Hospital (Approval number 2021-02-008BC). Competing Interests The authors have no relevant financial or non-financial interests to disclose. Data availability All data in our study are available from the corresponding authors upon reasonable request. References Adnan, A., & Basu, S. (2023). PSMA Receptor-Based PET-CT: The Basics and Current Status in Clinical and Research Applications. Diagnostics (Basel) , 13 (1). https://doi.org/10.3390/diagnostics13010158 Allach, Y., Banda, A., van Gemert, W., de Groot, M., Derks, Y., Schilham, M., Hoepping, A., Perk, L., Gotthardt, M., Janssen, M., Nagarajah, J., & Privé, B. M. (2022). 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R., Iranpour, N., Loubrie, S., Schlein, A., & Rakow-Penner, R. (2024). Application of PET/MRI in Gynecologic Malignancies. Cancers (Basel) , 16 (8). https://doi.org/10.3390/cancers16081478 Eiber, M., Fendler, W. P., Rowe, S. P., Calais, J., Hofman, M. S., Maurer, T., Schwarzenboeck, S. M., Kratowchil, C., Herrmann, K., & Giesel, F. L. (2017). Prostate-Specific Membrane Antigen Ligands for Imaging and Therapy. J Nucl Med , 58 (Suppl 2), 67s-76s. https://doi.org/10.2967/jnumed.116.186767 Fendler, W. P., Calais, J., Eiber, M., Flavell, R. R., Mishoe, A., Feng, F. Y., Nguyen, H. G., Reiter, R. E., Rettig, M. B., Okamoto, S., Emmett, L., Zacho, H. D., Ilhan, H., Wetter, A., Rischpler, C., Schoder, H., Burger, I. A., Gartmann, J., Smith, R., . . . Hope, T. A. (2019). Assessment of 68Ga-PSMA-11 PET Accuracy in Localizing Recurrent Prostate Cancer: A Prospective Single-Arm Clinical Trial. JAMA Oncol , 5 (6), 856-863. https://doi.org/10.1001/jamaoncol.2019.0096 Giesel, F. 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PET/MRI versus PET/CT in oncology: a prospective single-center study of 330 examinations focusing on implications for patient management and cost considerations. Eur J Nucl Med Mol Imaging , 47 (1), 51-60. https://doi.org/10.1007/s00259-019-04452-y Mojsak, M., Szumowski, P., Amelian, A., Hladunski, M., Kubas, B., Myśliwiec, J., Kochanowicz, J., & Moniuszko, M. (2023). Application of 18F-PSMA-1007 PET/MR Imaging in Early Biochemical Recurrence of Prostate Cancer: Results of a Prospective Study of 60 Patients with Very Low PSA Levels ≤ 0.5 ng/mL. Cancers (Basel) , 15 (16). https://doi.org/10.3390/cancers15164185 Morris, M. J., Rowe, S. P., Gorin, M. A., Saperstein, L., Pouliot, F., Josephson, D., Wong, J. Y. C., Pantel, A. R., Cho, S. Y., Gage, K. L., Piert, M., Iagaru, A., Pollard, J. H., Wong, V., Jensen, J., Lin, T., Stambler, N., Carroll, P. R., & Siegel, B. A. (2021). Diagnostic Performance of (18)F-DCFPyL-PET/CT in Men with Biochemically Recurrent Prostate Cancer: Results from the CONDOR Phase III, Multicenter Study. Clin Cancer Res , 27 (13), 3674-3682. https://doi.org/10.1158/1078-0432.Ccr-20-4573 Mottet, N., van den Bergh, R. C. N., Briers, E., Van den Broeck, T., Cumberbatch, M. G., De Santis, M., Fanti, S., Fossati, N., Gandaglia, G., Gillessen, S., Grivas, N., Grummet, J., Henry, A. M., van der Kwast, T. H., Lam, T. B., Lardas, M., Liew, M., Mason, M. D., Moris, L., . . . Cornford, P. (2021). EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer-2020 Update. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol , 79 (2), 243-262. https://doi.org/10.1016/j.eururo.2020.09.042 Perera, M., Papa, N., Christidis, D., Wetherell, D., Hofman, M. S., Murphy, D. G., Bolton, D., & Lawrentschuk, N. (2016). 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Front Oncol , 14 , 1373606. https://doi.org/10.3389/fonc.2024.1373606 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4571324","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":316998944,"identity":"0f136908-ce03-4dc7-9988-c6690f271347","order_by":0,"name":"Ko-Han Lin","email":"","orcid":"","institution":"Taipei Veterans General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ko-Han","middleName":"","lastName":"Lin","suffix":""},{"id":316998945,"identity":"ae9e73af-2109-4eca-a58f-9067e5072400","order_by":1,"name":"Tzu-Chun Wei","email":"","orcid":"","institution":"Taipei Veterans General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tzu-Chun","middleName":"","lastName":"Wei","suffix":""},{"id":316998948,"identity":"17f2e8c9-f765-4c4e-9c62-51a4d7268833","order_by":2,"name":"Shu-Huei Shen","email":"","orcid":"","institution":"Taipei Veterans General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shu-Huei","middleName":"","lastName":"Shen","suffix":""},{"id":316998949,"identity":"7043ad0e-d103-4f59-bca8-3bcbe7d85262","order_by":3,"name":"William Ji-Shien Huang","email":"","orcid":"","institution":"Taipei Veterans General Hospital","correspondingAuthor":false,"prefix":"","firstName":"William","middleName":"Ji-Shien","lastName":"Huang","suffix":""},{"id":316998951,"identity":"cb54f974-3fb7-4e93-aaf6-2223b900d8b4","order_by":4,"name":"Nan-Jing Peng","email":"","orcid":"","institution":"Taipei Veterans General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Nan-Jing","middleName":"","lastName":"Peng","suffix":""},{"id":316998952,"identity":"d47ec20c-31a3-4081-826e-b22cde0b07b3","order_by":5,"name":"Yuh-Feng Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/klEQVRIiWNgGAWjYDAC5gMg0kaOgYGHWC1sCSAyzRiohbEBKgZn4NNyKLGBaC0Gx3gMPxf8OpC+4fza448LKhjs+iUS2B/jcyRQi7H0zL47uRtuvEtsnnGGIXnmjATGZrxa7vdukObteZY7c8YZw2beNoZkgzMHGJtz8NrCu/k3b8/hdEmwln/EadkmzfPjcAI/fw9QSwODncHxBvxaJI/xf7PmbUgz7JfgMZw945hEgmR7Y+PsP3i08B1jS77N88dGno3/jMHnghobe35m5gMfZ+DRonAASDC2AQmJBAZmIAmMIAIxKQ+WBrmD/wBIC4M9XuWjYBSMglEwIgEA0oFUDfoGaHwAAAAASUVORK5CYII=","orcid":"","institution":"Taipei Veterans General Hospital","correspondingAuthor":true,"prefix":"","firstName":"Yuh-Feng","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2024-06-12 15:31:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4571324/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4571324/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":60185579,"identity":"65015c6d-8824-4eba-a6f1-65c639f4081d","added_by":"auto","created_at":"2024-07-12 18:42:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":5401261,"visible":true,"origin":"","legend":"\u003cp\u003eDemonstration of local recurrent lesions adjacent to the urinary wall detected using PSMA-PET study.\u003c/p\u003e\n\u003cp\u003e(A)-(C) A 67-year-old patient with PCa underwent a PSMA-PET study due to a gradual increase in PSA (0.39 ng/mL; PSAdt: 4.2 months). (A) Axial fused PSMA PET/MRI showed a lesion with intense and confluent PSMA uptake (SUVmax 12.3) in the posterior urinary bladder wall (yellow arrow). However, (B) T2WI-MRI and (C) the fusion image of DWI with T2WI-MRI identified two adjacent lesions (yellow arrows).\u003c/p\u003e\n\u003cp\u003e(D)-(F) An 81-year-old patient with PCa underwent a PSMA-PET study due to a gradual increase in PSA (0.23 ng/mL; PSAdt: 13.8 months). (D) Axial fused PSMA PET/MRI revealed a lesion with moderately increased PSMA uptake (SUVmax 3.27) in the posterior urinary bladder wall (red arrow). However, simultaneous (E) T2WI-MRI and (F) the fusion image of DWI with T2WI-MRI only showed vague signals (red dashed circles).\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-4571324/v1/d49abdcd0e3699a436ef6c5f.png"},{"id":60185580,"identity":"aeec98ae-b018-4a07-99a0-37892dd335d3","added_by":"auto","created_at":"2024-07-12 18:42:57","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":4484603,"visible":true,"origin":"","legend":"\u003cp\u003ePSMA-PET study for a 67-year-old patient with PCa who exhibited a gradual increase in PSA levels (0.26 ng/mL; PSAdt: 1.9 months).\u003c/p\u003e\n\u003cp\u003e(A) Axial PSMA PET; (B) fused PET with T2WI-MRI; and (C) axial T2WI-MRI. A focus of vague uptake (SUVmax 2.16) was noted adjacent to the right posterior bladder neck abutting the surgical anastomosis (yellow arrows). A PSMA-RADS score of 3 was assigned. A follow-up PSMA-PET study was performed 26 months later due to a progressive rise in PSA levels to 1.81 ng/mL. (D) Axial PSMA PET; (E) fused PET with T2WI-MRI; and (F) axial T2WI-MRI. The vague lesion exhibited progressive change in PSMA uptake (SUVmax 5.05) (red arrows). Local recurrence was confirmed, and the patient underwent targeted radiation therapy followed by ADT. However, simultaneous T2WI-MRI failed to detect this lesion in both the initial and follow-up scans (C, F) (yellow and red dashed circles).\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-4571324/v1/069a770087d4104552c132ff.png"},{"id":60185578,"identity":"28d9fb07-b5f5-40bb-abd1-93d3d2a7cf54","added_by":"auto","created_at":"2024-07-12 18:42:57","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":4461378,"visible":true,"origin":"","legend":"\u003cp\u003ePSAM-PET study for a 68-year-old patient with PCa who presented with a gradual increase in PSA levels (0.23 ng/mL; PSAdt: 4.6 months).\u003c/p\u003e\n\u003cp\u003e(A) Axial PSMA PET; (B) axial fused PET with TIWI-MRI; (C) coronal fused PET with T2WI-MRI; and (D) coronal T2WI-MRI. An indistinct lesion (SUVmax 2.8) was observed in right internal iliac region (yellow arrows). A PSMA-RADS score of 3 was assigned. A follow-up PSMA-PET was performed 15 months later due to a progressive rise in PSA levels to 0.48 ng/mL. Progressive changes in the right internal iliac lesion (SUVmax 7.3) were identified in the corresponding images (E-H, red arrows).\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-4571324/v1/eaecca573b45e8ed090a7e4f.png"},{"id":60185581,"identity":"0718df02-bcda-48fd-aa9e-210ade3c2553","added_by":"auto","created_at":"2024-07-12 18:42:57","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":2098940,"visible":true,"origin":"","legend":"\u003cp\u003ePSMA-PET study of a 78-year-old patient with PCa who presented with a gradual increase in PSA levels (0.4 ng/mL; PSAdt: 19 months).\u003c/p\u003e\n\u003cp\u003e(A) Sagittal fused PET/MRI; and (B) T2WI-MRI. An indistinct lesion (SUVmax 2.61) was observed in the sacrum (yellow arrows). A PSMA-RADS score of 3 was assigned. A follow-up PSMA-PET was conducted 26 months later due to a progressive rise in PSA levels to 1.09 ng/mL. Progressive changes in the sacral lesion (SUVmax 4.64) were identified in the corresponding images (C-D, red arrows).\u003c/p\u003e","description":"","filename":"Fig4.png","url":"https://assets-eu.researchsquare.com/files/rs-4571324/v1/160dae7874b891f365489a97.png"},{"id":60186955,"identity":"657cf9ac-5ad7-4e19-b221-d9471717103b","added_by":"auto","created_at":"2024-07-12 19:07:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":35087846,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4571324/v1/7c7b26f1-5a1b-4598-b359-eded0762df12.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"18F-PSMA-1007 PET/MR for Early Detection of Biochemical Recurrence of Prostate Cancer in Very Low (≤ 0.5 ng/mL) Prostate-Specific Antigen Levels","fulltext":[{"header":"Introduction","content":"\u003cp\u003eProstate cancer (PCa) remains a significant health concern for men globally, ranking as the second most commonly diagnosed cancer and the fifth leading cause of cancer-related deaths among men. In 2020, there were approximately 1,414,000 new cases and 375,304 deaths attributed to prostate cancer, underscoring its substantial impact on men's health worldwide and highlighting the ongoing need for effective diagnostic and therapeutic strategies to manage and reduce the burden of this disease (Sung et al., \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Wang et al., \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Despite advancements in early detection and treatment, managing PCa, particularly in its recurrence and/or metastases, continues to pose significant challenges. Recurrence and metastasis often require more complex and aggressive treatment approaches, emphasizing the critical need for continued research and development of advanced diagnostic tools and therapeutic methods to improve patient outcomes and manage the disease more effectively.\u003c/p\u003e \u003cp\u003eThe issue of PCa recurrence after primary treatment stands as a major concern, with biochemical recurrence (BCR) affecting 20\u0026ndash;50% of patients (Cornford et al., \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Mottet et al., \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). This underscores the importance of a nuanced approach to detection and management for improving patient outcomes. The American Urological Association and European Association of Urology have established guidelines for recognizing BCR, highlighting the role of prostate-specific antigen (PSA) levels in diagnosis (Simon et al., \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Typically, recurrence is indicated by a rise in PSA levels, defined as PSA reaching or exceeding 0.2 ng/mL post-prostatectomy or increasing by 2 ng/mL above the nadir after radiation therapy (Cookson et al., \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2007\u003c/span\u003e; Cornford et al., \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Managing patients with PCa who experience BCR following primary treatment is complex due to the challenge of balancing the prevention of clinical progression with the risk of over-treatment. Adjuvant therapy is reserved for at-risk patients, while recommendations for salvage therapy vary and lack definitive evidence. An individualized, multidisciplinary approach is essential, with advances in imaging techniques potentially improving future management (Artibani et al., \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2018\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn this context, molecular imaging techniques, particularly PET/CT scans using \u003csup\u003e18\u003c/sup\u003eF-Fluciclovine and prostate-specific membrane antigen (PSMA) radiotracers, have revolutionized the detection and management of recurrent PCa (Eiber et al., \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; Savir-Baruch \u0026amp; Schuster, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). \u003csup\u003e18\u003c/sup\u003eF-Fluciclovine, an amino acid analogue, has shown promise in identifying recurrent disease by localizing to prostate cancer cells via amino acid transporters (Marcus et al., \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). This modality has proven especially beneficial in patients with low serum PSA levels (\u0026le;\u0026thinsp;1 ng/mL), offering a new avenue for early detection and facilitating targeted salvage therapy (Andriole et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Clinical trials, such as the FALCON study, have highlighted its potential in improving PSA response compared to traditional methods (Scarsbrook et al., \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e2020\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOn the other hand, PSMA PET/CT imaging agent like \u003csup\u003e68\u003c/sup\u003eGa-PSMA-11 and \u003csup\u003e18\u003c/sup\u003eF-PSMA-1007, provides a high sensitivity and specificity for detecting both local and distant recurrences (Cornford et al., \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Giesel, Kesch, et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; Mottet et al., \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Perera et al., \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). These radiotracers have shown advantages over \u003csup\u003e18\u003c/sup\u003eF-Fluciclovine in certain aspects, particularly in detecting disease with minimal urinary bladder activity (Calais et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Pernthaler et al., \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2019\u003c/span\u003e), which is crucial for accurate localization. A meta-analysis comparing these modalities revealed pooled detection rates favoring PSMA PET/CT, especially in patients with very low PSA levels (\u0026lt;\u0026thinsp;0.5 ng/mL) (Tan et al., \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2020\u003c/span\u003e), suggesting its superior efficacy in early and precise disease localization.\u003c/p\u003e \u003cp\u003eThe continuous development of PET imaging technologies, including the introduction of simultaneous PET/MR scanners, represents a significant advancement in the diagnostic arsenal against PCa. PET/MR, combining the detailed anatomical imaging of MRI with the functional insights of PET, has demonstrated superiority in assessing local recurrence and lymph node involvement. This technology, particularly when combined with PSMA ligands, offers a comprehensive evaluation of recurrent disease, enhancing the potential for early intervention and personalized treatment strategies.\u003c/p\u003e \u003cp\u003eHowever, the struggle against recurrent PCa is increasingly being enhanced by revolutionary developments in diagnostic imaging technologies. Ongoing research and clinical trials are critical for identifying the best ways to use these technologies, moving clinicians closer to providing more effective, personalized care for patients with recurrent PCa. Consequently, our study is dedicated to evaluating the diagnostic efficacy of \u003csup\u003e18\u003c/sup\u003eF-PSMA-1007 PET/MR (PSMA-PET) in detecting early BCR at notably low PSA levels (\u0026le;\u0026thinsp;0.5 ng/mL), aiming to refine treatment approaches and improve patient outcomes.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient recruitment\u003c/h2\u003e \u003cp\u003eThis prospective study was conducted at a medical center in northern Taiwan, focusing on patients with histologically confirmed PCa and BCR following radical prostatectomy or radiation therapy. BCR was defined as a PSA level greater than 0.1 ng/mL measured more than six weeks after prostatectomy, or a PSA increase of more than 2 ng/mL above the nadir following external beam radiation therapy (EBRT) (Roach et al., \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2006\u003c/span\u003e; Shore et al., \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). All participants had undergone radical prostatectomy as a curative treatment. The study protocol was reviewed and approved by the Institutional Review Board of the study hospital (IRB #2021-02-008BC).\u003c/p\u003e \u003cp\u003e \u003csup\u003e \u003cb\u003e18\u003c/b\u003e \u003c/sup\u003e \u003cb\u003eF-PSMA-1007 PET/MRI protocol\u003c/b\u003e \u003c/p\u003e \u003cp\u003eParticipants were instructed to fast for at least 6 hours prior to undergoing the imaging procedures. The protocol began with an intravenous administration of the \u003csup\u003e18\u003c/sup\u003eF-PSMA-1007. The dosage was calculated based on the participant's body weight, at 4 MBq/kg, followed by simultaneous PET/MRI (SIGNA PET/MR, GE Healthcare, Waukesha, Wisconsin, USA) imaging covering the body from the thighs to the skull, commencing 90 minutes after the injection. This system uniquely combines 3T MR imaging capabilities with PET imaging, employing state-of-the-art silicon photomultipliers (SiPM) for enhanced photodetection.\u003c/p\u003e \u003cp\u003eThe PET data acquired were reconstructed into dynamic multi-frame images using a sophisticated three-dimensional time-of-flight (TOF)-enabled ordered subsets expectation maximization (OSEM) iterative algorithm. This process included the incorporation of a point-spread function kernel, which significantly improves the resolution of the images.\u003c/p\u003e \u003cp\u003eMultiparametric MRI (mpMRI) was began with axial T1-weighted images for a basic anatomy overview, followed by axial, sagittal, and coronal T2-weighted images for precise mapping of the prostate and surrounding areas. Axial diffusion-weighted imaging (DWI) with an apparent diffusion coefficient (ADC) map was used to identify potential cancer areas by detecting restricted diffusion. The study also included dynamic contrast-enhanced (DCE) MRI scans with a gadolinium-based contrast agent to examine the prostate's vascular patterns and enhance lesion visibility, capturing 30 dynamic phases. Furthermore, it expanded to whole-body MRI assessments, using DWI and 3D T1-weighted axial scans before and after contrast, to detect metastatic disease and provide a comprehensive view, highlighting the protocol's thorough approach in evaluating prostate cancer. The integrated PET and T1-weighted axial scan images were acquired for a thorough evaluation of prostate cancer, addressing both local tumor characteristics and potential disease spread. By combining PET with various MRI techniques, the aim was to offer a detailed, comprehensive view of the tumor, essential for formulating an effective treatment plan.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eImage analysis and strategies of patient management\u003c/h2\u003e \u003cp\u003eThe image analysis of the PET and mpMRI images in this study was conducted through a meticulous and collaborative approach. Initially, the mpMRI scans were subject to an independent review by a radiologist, tasked with the identification and staging of any tumors within the prostate. This crucial step laid the groundwork for further analysis. Following this initial examination, a collaborative assessment was undertaken, synthesizing of both a radiologist and a nuclear medicine physician.\u003c/p\u003e \u003cp\u003eLesions were classified under PSMA-RADS version 1.0 (Rowe et al., \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2018\u003c/span\u003e) ; categories 4 (high focal PSMA uptake at locations characteristic of prostate cancer without corresponding lesions on MR) and 5 (high focal PSMA uptake coincident with a definitive anatomic lesion on MR) were interpreted as positive findings. Subsequent treatment protocols were developed by the multidisciplinary team (MDT) specializing in PCa. Patients identified with these positive lesions underwent treatment with local EBRT plus short-term androgen deprivation therapy (ADT) for 26 individuals, local EBRT alone for 5 individuals, or ADT alone for 2 individuals. For those presenting with equivocal (PSMA-RADS 3A or 3B) or negative findings, a minimum follow-up period of 12 months (ranging between 14 to 30 months) was implemented, alongside imaging assessments (via PSMA-PET or mpMRI) to monitor any progression or changes. Nevertheless, not all participants underwent histopathological verification of their results.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec6\"\u003e\n \u003ch2\u003ePatient Demographics and PSA Characteristics\u003c/h2\u003e\n \u003cp\u003eFrom May 2021 to January 2023, 157 patients with histology-proven PCa and BCR after radical prostatectomy or radiation therapy were recruited for this study. Among these patients, the results of 54 patients whose PSA\u0026thinsp;\u0026le;\u0026thinsp;0.5 ng/mL (mean: 0.34\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1 ng/mL; range 0.11\u0026ndash;0.50 ng/mL) were retrospectively reviewed and analyzed. Two patients, despite with positive findings, were excluded from the analysis because the result still inclusive after one and a half-year follow-up. Finally, 52 patients were enrolled in this study. The pathologic stagings were pT2N0M0 (n\u0026thinsp;=\u0026thinsp;16), T3aN0M0 (n\u0026thinsp;=\u0026thinsp;24), pT3N0M0 (n\u0026thinsp;=\u0026thinsp;11), and pT3aN1M0 (n\u0026thinsp;=\u0026thinsp;1).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\"\u003e\n \u003ch2\u003ePSMA-PET Detection Rate and Comparison with mpMRI\u003c/h2\u003e\n \u003cp\u003eThe PSMA-PET imaging demonstrated a high detection rate in patients with low PSA levels. Out of the 52 patients, 33 were confirmed positive by PSMA-PET, resulting in a detection rate of 63.5%. This substantial detection rate is particularly noteworthy given the low PSA levels (\u0026le;\u0026thinsp;0.5 ng/mL) in the cohort, highlighting the sensitivity of PSMA-PET for early detection of recurrent PCa.\u003c/p\u003e\n \u003cp\u003eSimultaneous mpMRI yielded negative findings in nine of these 33 PSMA-PET positive patients. This discrepancy suggests that PSMA-PET may detect lesions that mpMRI fails to identify, emphasizing the enhanced sensitivity of PSMA-PET imaging (Fig. \u003cspan\u003e1\u003c/span\u003e). Comparative analysis revealed that patients with positive PSMA-PET results had significantly higher PSA levels (0.36\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10 ng/mL) compared to those with negative findings (0.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11 ng/mL) (p\u0026thinsp;=\u0026thinsp;0.014) (Table \u003cspan\u003e1\u003c/span\u003e). However, no statistically significant correlation was observed between PSA doubling-time (PSAdt) and PSMA-PET results (p\u0026thinsp;=\u0026thinsp;0.32), indicating that PSAdt does not significantly impact the detection capability of PSMA-PET in this patient population.\u003c/p\u003e\n \u003cp\u003e(D)-(F) An 81-year-old patient with PCa underwent a PSMA-PET study due to a gradual increase in PSA (0.23 ng/mL; PSAdt: 13.8 months). (D) Axial fused PSMA PET/MRI revealed a lesion with moderately increased PSMA uptake (SUVmax 3.27) in the posterior urinary bladder wall (red arrow). However, simultaneous (E) T2WI-MRI and (F) the fusion image of DWI with T2WI-MRI only showed vague signals (red dashed circles).\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 1\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eGleason Scores and PSA Doubling Time in Patients with Positive and Negative PSMA-PET Results\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"3\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePSMA-PET (+), n\u0026thinsp;=\u0026thinsp;33\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePSMA-PET (-), n\u0026thinsp;=\u0026thinsp;19\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGS\u0026thinsp;\u0026lt;\u0026thinsp;7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGS\u0026thinsp;=\u0026thinsp;7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGS\u0026thinsp;\u0026gt;\u0026thinsp;7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePSAdt\u0026thinsp;\u0026le;\u0026thinsp;6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePSAdt\u0026thinsp;\u0026gt;\u0026thinsp;6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean PSA (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.36\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10 (0.19\u0026ndash;0.5)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11 (0.11\u0026ndash;0.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean PSAdt (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.59\u0026thinsp;\u0026plusmn;\u0026thinsp;6.44 (2.9\u0026ndash;27.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.05\u0026thinsp;\u0026plusmn;\u0026thinsp;6.38 (1.9\u0026ndash;21.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eGS\u0026thinsp;=\u0026thinsp;Gleason Scores, PSA\u0026thinsp;=\u0026thinsp;prostate-specific antigen, PSAdt\u0026thinsp;=\u0026thinsp;PSA Doubling Time, PSMA-PET\u0026thinsp;=\u0026thinsp;\u003csup\u003e18\u003c/sup\u003eF-PSMA-1007 PET/MR.\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e*p\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.009\u003c/p\u003e\n \u003cp\u003eFurther analysis of the patients with positive and negative PSMA-PET results, showed a distinct distribution of Gleason scores (GS) and PSAdt (Table \u003cspan\u003e1\u003c/span\u003e). Among the PSMA-PET positive group, 26 patients had a GS of 7, while 7 had a GS\u0026thinsp;\u0026gt;\u0026thinsp;7. The mean PSAdt was slightly higher in the PSMA-PET positive group (9.59\u0026thinsp;\u0026plusmn;\u0026thinsp;6.44 months) compared to the negative group (9.05\u0026thinsp;\u0026plusmn;\u0026thinsp;6.38 months).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\"\u003e\n \u003ch2\u003eLocal Recurrence and Metastatic Findings\u003c/h2\u003e\n \u003cp\u003ePSMA-PET imaging identified 34 local recurrent lesions in 31 patients, accounting for 59.6% of the cohort. The majority of these lesions (56%) were located at anastomotic sites. The reduced urinary activity associated with \u003csup\u003e18\u003c/sup\u003eF-PSMA-1007 facilitated the clear detection of seven lesions near the urinary bladder wall, which constituted 20% of the findings. Additionally, one lesion adjacent to the posterior urinary bladder wall was accurately identified as a recurrence in the vas deferens.\u003c/p\u003e\n \u003cp\u003ePSMA-PET imaging detected 12 metastatic lymph nodes in 10 patients, representing 24% of all detected lesions. All metastatic lymph nodes were confined to the pelvic cavity, with no extra-pelvic detections. The short-axis diameter of these lymph nodes ranged from 2 to 8 mm. Notably, one lymph node categorized under PSMA-RADS category 5 had a short-axis diameter of 8 mm and a maximum standardized uptake value (SUVmax) of 16.69. Furthermore, six patients with nodal metastases were concurrently identified with local recurrences.\u003c/p\u003e\n \u003cp\u003eFour skeletal metastases were detected in four patients, representing 8% of all detected lesions. These metastases were located within the pelvis and included two lesions classified as PSMA-RADS category 5, one as category 4, and one as category 3 (Table \u003cspan\u003e2\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 2\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eDetection of Lesions and SUVmax in Various Recurrence Sites\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"3\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRecurrence Site\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNo. of detected lesions (No. of patients)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMean SUVmax\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (Range)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLocal recurrence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34 (31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.25\u0026thinsp;\u0026plusmn;\u0026thinsp;3.72 (2.5\u0026ndash;17.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnastomosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.51\u0026thinsp;\u0026plusmn;\u0026thinsp;3.97 (2.5\u0026ndash;17.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUrinary bladder wall\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.83\u0026thinsp;\u0026plusmn;\u0026thinsp;4.26 (3.01\u0026ndash;14.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSeminal vesicle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.03\u0026thinsp;\u0026plusmn;\u0026thinsp;2.80 (2.63\u0026ndash;9.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVas deferans\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePerirectal space\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePelvic floor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePelvic lymph nodes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.80\u0026thinsp;\u0026plusmn;\u0026thinsp;6.62 (2.35\u0026ndash;22.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBone metastasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.51\u0026thinsp;\u0026plusmn;\u0026thinsp;1.46 (1.5\u0026ndash;5.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eSUVmax\u0026thinsp;=\u0026thinsp;maximum standardized uptake value, SD\u0026thinsp;=\u0026thinsp;standard deviation.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\"\u003e\n \u003ch2\u003eLongitudinal Follow-Up and Reclassification\u003c/h2\u003e\n \u003cp\u003eThe longitudinal follow-up and reclassification of initially equivocal lesions (PSMA-RADS score 3) underscored the dynamic nature of recurrent prostate cancer and the importance of continuous monitoring. During the retrospective analysis, initially equivocal lesions were found to be positive in five patients upon follow-up scans conducted 14\u0026ndash;26 months later. This reclassification increased the detection rate from 63.5\u0026ndash;73.1%, demonstrating the importance of longitudinal monitoring in patients with indeterminate initial findings.\u003c/p\u003e\n \u003cp\u003eTable \u003cspan\u003e3\u003c/span\u003e details the characteristics of these reclassified lesions, including their locations, PSA levels, PSAdt, and SUVmax values. For instance, one patient (#1) initially had an equivocal lesion at the anastomosis with a PSA of 0.26 ng/mL and a PSAdt of 1.9 months. Upon re-evaluation 26 months later, this lesion was confirmed as positive with a SUVmax of 2.5. Similarly, patient #2 had an equivocal lesion near the urinary bladder wall with a PSA of 0.23 ng/mL and a PSAdt of 2.4 months, which was later confirmed as positive through mpMRI with a SUVmax of 3.82 after 12 months.\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 3\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eReclassification of Initially Equivocal (Category 3) Lesions as True-positive on Follow-up\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"7\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePatient No.\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eLocation\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePSA\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePSAdt\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSUVmax\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eModality\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eInterval\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e#1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnastomosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePSMA-PET\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26 m\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e#2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUrinary bladder wall\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003empMRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 m\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e#3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRight external iliac node\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePSMA-PET\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 m\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e#4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRight internal iliac node\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePSMA-PET\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 m\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e#5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSacrum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19 m\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePSMA-PET\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26 m\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003ePSA\u0026thinsp;=\u0026thinsp;prostate-specific antigen, PSAdt\u0026thinsp;=\u0026thinsp;PSA Doubling Time, SUVmax\u0026thinsp;=\u0026thinsp;maximum standardized uptake value, PSMA-PET\u0026thinsp;=\u0026thinsp;\u003csup\u003e18\u003c/sup\u003eF-PSMA-1007 PET/MR, mpMRI\u0026thinsp;=\u0026thinsp;multiparametric MRI, m\u0026thinsp;=\u0026thinsp;month.\u003c/p\u003e\n \u003cp\u003eThe reclassification of initially equivocal lesions as true positives upon follow-up also validates the need for ongoing research and development of more sensitive imaging technologies. These findings suggest that PSMA-PET imaging can significantly improve patient outcomes by enabling earlier detection and intervention, ultimately reducing the burden of recurrent prostate cancer.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\"\u003e\n \u003ch2\u003eStatistical Analysis and Correlations\u003c/h2\u003e\n \u003cp\u003eIn-depth statistical analysis was performed to understand the relationships between various clinical parameters and the efficacy of PSMA-PET imaging. No significant correlation was found between PSAdt and the detection rate of PSMA-PET (p\u0026thinsp;=\u0026thinsp;0.32), suggesting that the rate of PSA increase is not a determining factor for the sensitivity of PSMA-PET in detecting recurrent lesions at low PSA levels. Furthermore, the analysis showed no significant correlations between PSA level-SUVmax and PSAdt-SUVmax of the detected lesions (p\u0026thinsp;=\u0026thinsp;0.85 and 0.20, respectively). This indicates that the SUVmax, which measures the intensity of radiotracer uptake, is not influenced by PSA kinetics, reaffirming the robustness of PSMA-PET imaging irrespective of PSA dynamics (Table \u003cspan\u003e4\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 4\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eComparison of Clinical Characteristics Between Patients with Positive and Negative PSMA-PET Results\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"3\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePSMA-PET (+)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePSMA-PET (-)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePatients\u0026rsquo; No\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGS\u0026thinsp;\u0026lt;\u0026thinsp;7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGS\u0026thinsp;=\u0026thinsp;7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGS\u0026thinsp;\u0026gt;\u0026thinsp;7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePSAdt\u0026thinsp;\u0026le;\u0026thinsp;6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePSAdt\u0026thinsp;\u0026gt;\u0026thinsp;6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean PSA (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.36\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10 (0.19\u0026ndash;0.5)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09 (0.11\u0026ndash;0.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean PSAdt (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.15\u0026thinsp;\u0026plusmn;\u0026thinsp;6.54 (1.9\u0026ndash;27.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.06\u0026thinsp;\u0026plusmn;\u0026thinsp;6.02 (4.5\u0026ndash;21.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eGS\u0026thinsp;=\u0026thinsp;Gleason Scores, PSA\u0026thinsp;=\u0026thinsp;prostate-specific antigen, PSAdt\u0026thinsp;=\u0026thinsp;PSA Doubling Time, PSMA-PET\u0026thinsp;=\u0026thinsp;\u003csup\u003e18\u003c/sup\u003eF-PSMA-1007 PET/MR.\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e*p\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.014\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur research demonstrates a remarkable detection rate of up to 63.5% for PSMA-PET in patients with PSA levels below 0.5 ng/mL. This high detection rate underscores the significant diagnostic value of PSMA-PET imaging in identifying recurrent PCa even at very low PSA levels. Upon retrospective investigation of these cases two years post the initial PSMA-PET scans, we found that initially equivocal lesions (PSMA-RADS score 3) were confirmed positive in five patients, raising the detection rate to 73.1%. This highlights the sustained efficacy of this imaging modality in detecting disease recurrence over time and emphasizes the necessity of follow-up imaging in cases with initially indeterminate results. Moreover, outcomes from PSMA-PET imaging significantly influence personalized treatment strategies, impacting clinical decisions for 17% of the participants in our investigation.\u003c/p\u003e\n\u003cp\u003eThe findings from our study carry several important clinical implications. Firstly, the detection of very small lesions with mild uptake initially categorized as equivocal highlights the challenges inherent in PSMA-PET imaging at low PSA levels. For instance, one patient (Table \u003cspan\u003e3\u003c/span\u003e, patient #1) had very small lesions with slight elevation in uptake, making definitive categorization difficult. Follow-up PSMA-PET scans after two years showed a significant rise in tracer uptake, confirming their pathological nature (Fig. \u003cspan\u003e2\u003c/span\u003e). This underscores the importance of expertise in interpreting PSMA-PET scans and the potential benefits of repeated imaging to capture the dynamic nature of PCa recurrence. In another case (Table \u003cspan\u003e3\u003c/span\u003e, patient #2), high urine activity hindered the accurate interpretation of the initial scan. A distinct lesion identified in a subsequent MRI study became visible upon review of the initial PSMA-PET scan, which had been obscured by urine activity. This emphasizes the critical role of complementary imaging modalities and the necessity for radiologists to be vigilant about potential artifacts that may obscure true-positive findings in PSMA-PET scans. Moreover, the confirmation of very small lymph nodes and skeletal metastases upon follow-up imaging demonstrates the importance of meticulous image analysis. Two patients (Table \u003cspan\u003e3\u003c/span\u003e, patient #3, #4) had small lymph nodes that initially raised suspicion but were not definitively identified as pathological. Follow-up PSMA-PET scans conducted two years later confirmed these as lymph node metastases (Fig. \u003cspan\u003e3\u003c/span\u003e). Similarly, small sacral lesions detected initially were later confirmed as metastatic in follow-up scans (Table \u003cspan\u003e3\u003c/span\u003e, patient #5) (Fig. \u003cspan\u003e4\u003c/span\u003e). These cases highlight the need for follow-up imaging to confirm and validate initial suspicions, especially for small and difficult-to-interpret lesions.\u003c/p\u003e\n\u003cp\u003ePrevious literature data indicate that the detection rates for PSA levels below 0.5 ng/mL are approximately 38\u0026ndash;45% for \u003csup\u003e68\u003c/sup\u003eGa-PSMA-11 (Fendler et al., \u003cspan\u003e2019\u003c/span\u003e; Kuppermann et al., \u003cspan\u003e2022\u003c/span\u003e). The unique hepatobiliary excretion pathway of \u003csup\u003e18\u003c/sup\u003eF-PSMA-1007, in contrast to the renal excretion observed with \u003csup\u003e68\u003c/sup\u003eGa-PSMA-11, results in clearer imaging of the pelvic region (Allach et al., \u003cspan\u003e2022\u003c/span\u003e; Giesel, Hadaschik, et al., \u003cspan\u003e2017\u003c/span\u003e). This reduced interference is critical for identifying local recurrences near the bladder and urethra, areas where conventional imaging techniques often face challenges due to tracer accumulation in the urine. Furthermore, the integration of PET and MR imaging technologies enhances overall diagnostic precision (Mayerhoefer et al., \u003cspan\u003e2020\u003c/span\u003e; Pichler et al., \u003cspan\u003e2008\u003c/span\u003e). MR imaging is renowned for its exceptional soft tissue contrast, which, when combined with the functional imaging capabilities of PET, enables a more comprehensive evaluation of pelvic lesions (Ebrahimi et al., \u003cspan\u003e2024\u003c/span\u003e). Consequently, PSMA-PET offers a more precise visualization of the pelvic region, facilitating well-informed clinical decisions. Our study also highlights the advantages of \u003csup\u003e18\u003c/sup\u003eF-PSMA-1007 over other radiotracers, such as \u003csup\u003e68\u003c/sup\u003eGa-PSMA-11, particularly in patients with low PSA levels. The unique hepatobiliary excretion pathway of \u003csup\u003e18\u003c/sup\u003eF-PSMA-1007 reduces interference from urinary activity, facilitating clearer imaging of the pelvic region and improving the detection of local recurrences near the bladder and urethra. This characteristic is crucial for accurate localization of recurrent disease and supports the integration of PSMA-PET into routine clinical practice for managing BCR of PCa. The superior imaging quality provided by \u003csup\u003e18\u003c/sup\u003eF-PSMA-1007 enables more precise interventions and potentially improves patient outcomes by allowing for more accurate treatment planning (Awenat et al., \u003cspan\u003e2021\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eWhen comparing \u003csup\u003e18\u003c/sup\u003eF-PSMA-1007 with other \u003csup\u003e18\u003c/sup\u003eF-labeled PSMA tracers such as \u003csup\u003e18\u003c/sup\u003eF-DCFPyL and \u003csup\u003e18\u003c/sup\u003eF-rhPSMA-7, it is important to consider their respective strengths and limitations. \u003csup\u003e18\u003c/sup\u003eF-PSMA-1007 offers the advantage of minimal renal excretion, which reduces urinary bladder activity and thus improves pelvic imaging clarity. However, \u003csup\u003e18\u003c/sup\u003eF-DCFPyL, which is predominantly excreted through the kidneys, may have higher sensitivity in detecting lesions in areas less affected by urinary activity but can be more challenging for pelvic imaging due to higher urinary excretion. Additionally, \u003csup\u003e18\u003c/sup\u003eF-DCFPyL has shown effectiveness in detecting liver metastases, making it particularly useful in scenarios where liver involvement is suspected (Giesel et al., \u003cspan\u003e2018\u003c/span\u003e). Similarly, \u003csup\u003e18\u003c/sup\u003eF-rhPSMA-7 combines the benefits of both renal and hepatobiliary excretion, which can be advantageous for detecting lesions across various regions but may still present challenges in pelvic imaging similar to those of \u003csup\u003e18\u003c/sup\u003eF-DCFPyL. The renal clearance can lead to higher urinary activity, which may obscure lesions near the bladder and ureters, but hepatobiliary excretion can mitigate some of these issues by reducing urinary interference, improving image quality in other regions (Wurzer et al., \u003cspan\u003e2020\u003c/span\u003e). In addition, \u003csup\u003e18\u003c/sup\u003eF-DCFPyL has been noted for its high tumor uptake and favorable biodistribution, making it a strong candidate for whole-body imaging (Morris et al., \u003cspan\u003e2021\u003c/span\u003e; Pienta et al., \u003cspan\u003e2021\u003c/span\u003e; Song et al., \u003cspan\u003e2022\u003c/span\u003e; Wurzer et al., \u003cspan\u003e2020\u003c/span\u003e). Each tracer thus has unique benefits, with \u003csup\u003e18\u003c/sup\u003eF-PSMA-1007 being highly effective for detailed pelvic imaging, \u003csup\u003e18\u003c/sup\u003eF-DCFPyL for its overall sensitivity and whole-body imaging capabilities, and \u003csup\u003e18\u003c/sup\u003eF-rhPSMA-7 for its balanced excretion properties (Song et al., \u003cspan\u003e2022\u003c/span\u003e). Nevertheless, \u003csup\u003e18\u003c/sup\u003eF-PSMA-1007\u0026apos;s minimal renal excretion makes it particularly advantageous for pelvic imaging by minimizing urinary interference, thereby enhancing the clarity and accuracy of detecting local recurrences.\u003c/p\u003e\n\u003cp\u003eThe absence of significant correlations between these variables highlights the complexity of PCa recurrence and the multifactorial nature of its detection. This indicates that PSMA-PET imaging may be influenced by various biological and technical factors that require an integrated approach for accurate assessment. The multifactorial nature of PCa recurrence necessitates comprehensive diagnostic strategies that encompass clinical, biochemical, and advanced imaging data. These integrated approaches are essential for providing a thorough assessment of recurrent disease and tailoring individualized treatment plans. The findings from our statistical analysis reinforce the reliability of PSMA-PET imaging as an independent diagnostic tool that can effectively detect recurrent PCa across a spectrum of PSA dynamics. This independence from PSA kinetics underscores the robustness of PSMA-PET imaging and its utility in a diverse range of clinical scenarios. Furthermore, the lack of correlation with PSA kinetics suggests that PSMA-PET could be particularly useful in cases where PSA levels alone do not provide a clear picture of disease status, thereby enhancing the overall diagnostic process.\u003c/p\u003e\n\u003cp\u003eMoreover, the significant impact of PSMA-PET imaging on personalized treatment strategies is evident from our findings (Yan et al., \u003cspan\u003e2024\u003c/span\u003e). The detection of recurrent disease at low PSA levels allows for timely and targeted interventions, such as local EBRT and ADT, which can significantly improve patient outcomes (Harsini et al., \u003cspan\u003e2023\u003c/span\u003e; Yan et al., \u003cspan\u003e2024\u003c/span\u003e). The treatment based on precise localization and characterization of recurrent lesions underscores the value of PSMA-PET imaging in the clinical management of PCa. By enabling early detection and accurate staging, PSMA-PET imaging facilitates the development of personalized treatment plans that are tailored to the specific needs and conditions of each patient, thereby enhancing the effectiveness of therapeutic interventions (Adnan \u0026amp; Basu, 2023; Gillette et al., \u003cspan\u003e2023\u003c/span\u003e). Additionally, this approach minimizes unnecessary treatments and reduces potential side effects by focusing on targeted therapy, thereby improving the quality of life for patients. The precision of PSMA-PET imaging also supports ongoing monitoring and timely adjustments to treatment plans, which is crucial for managing recurrent PCa effectively.\u003c/p\u003e\n\u003cp\u003eBoth PSMA PET/MR and PSMA PET/CT have their unique advantages and limitations. PET/CT is widely available and typically faster, providing both metabolic and anatomic information which is crucial for initial staging and restaging of prostate cancer. The CT component, however, exposes patients to ionizing radiation and offers limited soft tissue contrast, which can be a limitation in certain clinical scenarios (Awenat et al., \u003cspan\u003e2021\u003c/span\u003e). On the other hand, PET/MR offers superior soft tissue contrast due to the MRI component, which can be particularly advantageous in assessing local recurrences and pelvic lesions (Glemser et al., \u003cspan\u003e2022\u003c/span\u003e; Mojsak et al., \u003cspan\u003e2023\u003c/span\u003e). Additionally, MRI does not involve ionizing radiation, making it a safer option for repeated imaging, especially in younger patients or those requiring frequent follow-up scans. However, PET/MR is less available, more expensive, and generally takes longer than PET/CT, which may limit its use in some clinical settings. The choice between PET/CT and PET/MR should be based on the specific clinical scenario, patient characteristics, and the available resources, with PET/MR being preferable for detailed soft tissue evaluation and PET/CT for its accessibility and speed.\u003c/p\u003e\n\u003cp\u003eDespite the promising results, our study has several limitations that should be noted. First, the sample size was relatively small, with only 52 patients included in the final analysis. This limited number may affect the generalizability of our findings to a broader population of patients of PCa with BCR. Second, our study was conducted at a single medical center in northern Taiwan, which may introduce selection bias and limit the applicability of the results to other settings or populations with different demographic or clinical characteristics. Third, not all participants underwent histopathological verification of their PSMA-PET or mpMRI results. This lack of confirmatory pathology could lead to potential misclassification of lesions and affect the accuracy of our findings. Fourth, while PSMA-PET demonstrated a high detection rate, the impact of false-positive results cannot be entirely ruled out, particularly in the context of very low PSA levels where non-specific uptake might occur. Finally, the retrospective nature of the follow-up for initially equivocal lesions could introduce bias and affect the interpretation of the dynamic changes observed in these lesions. Further prospective studies with larger cohorts and multi-center involvement are warranted to validate our findings and refine the clinical utility of PSMA-PET imaging in the management of recurrent PCa.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur study revealed that, the use of PSMA-PET significantly enhances the detection of recurrent PCa at low PSA levels (\u0026le;\u0026thinsp;0.5 ng/mL), providing precise localized anatomical and functional insights that enhance clinical decision-making. The integration of this advanced imaging modality into clinical practice has the potential to significantly improve patient outcomes through early detection and personalized treatment approaches. Further research and longitudinal studies are essential to optimize its application and validate its long-term efficacy in managing BCR of PCa. The continued evolution of PSMA-PET imaging techniques and their integration with other diagnostic modalities will likely play a pivotal role in advancing the management of recurrent PCa, ultimately leading to better patient care and improved survival rates.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e \u003cem\u003eAll authors contributed to the study conception and design.\u0026nbsp;\u003c/em\u003eImage acquisition, interpreting, and data analysis were performed by Ko-Han Lin,\u0026nbsp;Tzu-Chun Wei, and Shu-Huei Shen. The first draft of the manuscript was written by Ko-Han Lin and Yuh-Feng Wang.\u0026nbsp;William Ji-Shien Huang and\u0026nbsp;Nan-Jing Peng supervised the writing of the manuscript.\u0026nbsp;Revision and final version of the manuscript were written by\u0026nbsp;Yuh-Feng Wang. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e This research was supported by the grant of\u0026nbsp;Taipei Veterans General Hospital\u0026nbsp;(V111E-008-1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e This study was approved by the\u0026nbsp;Institutional Review Board\u0026nbsp;of the\u0026nbsp;Taipei Veterans General Hospital\u0026nbsp;(Approval number\u0026nbsp;2021-02-008BC).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u0026nbsp;\u003c/strong\u003e\u003cem\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e All data in our study are available from the corresponding authors upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAdnan, A., \u0026amp; Basu, S. (2023). PSMA Receptor-Based PET-CT: The Basics and Current Status in Clinical and Research Applications. \u003cem\u003eDiagnostics (Basel)\u003c/em\u003e,\u003cem\u003e 13\u003c/em\u003e(1). https://doi.org/10.3390/diagnostics13010158 \u003c/li\u003e\n\u003cli\u003eAllach, Y., Banda, A., van Gemert, W., de Groot, M., Derks, Y., Schilham, M., Hoepping, A., Perk, L., Gotthardt, M., Janssen, M., Nagarajah, J., \u0026amp; Priv\u0026eacute;, B. M. (2022). An Explorative Study of the Incidental High Renal Excretion of [(18)F]PSMA-1007 for Prostate Cancer PET/CT Imaging. \u003cem\u003eCancers (Basel)\u003c/em\u003e,\u003cem\u003e 14\u003c/em\u003e(9). https://doi.org/10.3390/cancers14092076 \u003c/li\u003e\n\u003cli\u003eAndriole, G. L., Kostakoglu, L., Chau, A., Duan, F., Mahmood, U., Mankoff, D. A., Schuster, D. M., \u0026amp; Siegel, B. A. (2019). The Impact of Positron Emission Tomography with 18F-Fluciclovine on the Treatment of Biochemical Recurrence of Prostate Cancer: Results from the LOCATE Trial. \u003cem\u003eJ Urol\u003c/em\u003e,\u003cem\u003e 201\u003c/em\u003e(2), 322-331. https://doi.org/10.1016/j.juro.2018.08.050 \u003c/li\u003e\n\u003cli\u003eArtibani, W., Porcaro, A. B., De Marco, V., Cerruto, M. A., \u0026amp; Siracusano, S. (2018). Management of Biochemical Recurrence after Primary Curative Treatment for Prostate Cancer: A Review. \u003cem\u003eUrol Int\u003c/em\u003e,\u003cem\u003e 100\u003c/em\u003e(3), 251-262. https://doi.org/10.1159/000481438 \u003c/li\u003e\n\u003cli\u003eAwenat, S., Piccardo, A., Carvoeiras, P., Signore, G., Giovanella, L., Prior, J. O., \u0026amp; Treglia, G. (2021). 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Advancements in PSMA ligand radiolabeling for diagnosis and treatment of prostate cancer: a systematic review. \u003cem\u003eFront Oncol\u003c/em\u003e,\u003cem\u003e 14\u003c/em\u003e, 1373606. https://doi.org/10.3389/fonc.2024.1373606 \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"prostate cancer, PSA, biochemical recurrence, 18F-PSMA-1007, PET/MR","lastPublishedDoi":"10.21203/rs.3.rs-4571324/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4571324/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eTo evaluate the diagnostic efficacy of \u003csup\u003e18\u003c/sup\u003eF-PSMA-1007 PET/MR (PSMA-PET) in detecting biochemical recurrence (BCR) of prostate cancer (PCa) at very low (\u0026le;\u0026thinsp;0.5 ng/mL) prostate-specific antigen (PSA) levels.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe recruited 157 PCa patients with BCR post-radical prostatectomy or radiation therapy between May 2021 and January 2023. Among them, 52 patients with PSA\u0026thinsp;\u0026le;\u0026thinsp;0.5 ng/mL underwent PSMA-PET imaging. The imaging protocol included multiparametric MRI (mpMRI) and PET data analysis, with lesion classification based on PSMA-RADS version 1.0.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe PSMA-PET imaging demonstrated a 63.5% detection rate for recurrent PCa in patients with low PSA levels. PSMA-PET detected 34 local recurrent lesions, 12 metastatic lymph nodes, and 4 skeletal metastases. Follow-up imaging reclassified initially equivocal lesions, increasing the detection rate to 73.1%. Outcomes from PSMA-PET imaging significantly influenced personalized treatment strategies, impacting clinical decisions for 17% of the participants in our investigation.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003ePSMA-PET significantly enhances the detection of recurrent PCa at low PSA levels, providing precise localization and aiding in personalized treatment strategies. Further research is essential to optimize its clinical application and validate long-term efficacy.\u003c/p\u003e","manuscriptTitle":"18F-PSMA-1007 PET/MR for Early Detection of Biochemical Recurrence of Prostate Cancer in Very Low (≤ 0.5 ng/mL) Prostate-Specific Antigen Levels","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-12 18:42:52","doi":"10.21203/rs.3.rs-4571324/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f86c7bd6-e241-4ee3-96f8-e763bb8bc314","owner":[],"postedDate":"July 12th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-07-12T18:42:55+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-12 18:42:52","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4571324","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4571324","identity":"rs-4571324","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}