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Purpose: The aim of this study was to systematically evaluate the effect of thresholding algorithms used in computer vision for the quantification of prostate-specific membrane antigen positron emission tomography (PET) derived tumor volume (PSMA-TV) in patients with advanced prostate cancer. The results were validated with respect to the prognostication of overall survival in patients with advanced-stage prostate cancer., Materials and Methods: A total of 78 patients who underwent [ 177 Lu]Lu-PSMA-617 radionuclide therapy from January 2018 to December 2020 were retrospectively included in this study. [ 68 Ga]Ga-PSMA-11 PET images, acquired prior to radionuclide therapy, were used for the analysis of thresholding algorithms. All PET images were first analyzed semi-automatically using a pre-evaluated, proprietary software solution as the baseline method. Subsequently, five histogram-based thresholding methods and two local adaptive thresholding methods that are well established in computer vision were applied to quantify molecular tumor volume. The resulting whole-body molecular tumor volumes were validated with respect to the prognostication of overall patient survival as well as their statistical correlation to the baseline methods and their performance on standardized phantom scans., Results: The whole-body PSMA-TVs, quantified using different thresholding methods, demonstrate a high positive correlation with the baseline methods. We observed the highest correlation with generalized histogram thresholding (GHT) (Pearson r (r), p value (p): r = 0.977, p < 0.001) and Sauvola thresholding (r = 0.974, p < 0.001) and the lowest correlation with Multiotsu (r = 0.877, p < 0.001) and Yen thresholding methods (r = 0.878, p < 0.001). The median survival time of all patients was 9.87 months (95% CI [9.3 to 10.13]). Stratification by median whole-body PSMA-TV resulted in a median survival time from 11.8 to 13.5 months for the patient group with lower tumor burden and 6.5 to 6.6 months for the patient group with higher tumor burden. The patient group with lower tumor burden had significantly higher probability of survival (p < 0.00625) in eight out of nine thresholding methods (Fig. 2); those methods were SUVmax50 (p = 0.0038), SUV ≥3 (p = 0.0034), Multiotsu (p = 0.0015), Yen (p = 0.0015), Niblack (p = 0.001), Sauvola (p = 0.0001), Otsu (p = 0.0053), and Li thresholding (p = 0.0053)., Conclusion: Thresholding methods commonly used in computer vision are promising tools for the semiautomatic quantification of whole-body PSMA-TV in [ 68 Ga]Ga-PSMA-11-PET. The proposed algorithm-driven thresholding strategy is less arbitrary and less prone to biases than thresholding with predefined values, potentially improving the application of whole-body PSMA-TV as an imaging biomarker., (© 2023. The Author(s).)

The field of radioligand therapy has advanced greatly in recent years, driven largely by β-emitting therapies targeting somatostatin receptor-expressing tumors and the prostate-specific membrane antigen. Now, more clinical trials are under way to evaluate α-emitting targeted therapies as potential next-generation theranostics with even higher efficacy due to their high linear energy and short range in human tissues. In this review, we summarize the important studies ranging from the first Food and Drug Administration-approved α-therapy, 223 Ra-dichloride, for treatment of bone metastases in castration-resistant prostate cancer, including concepts in clinical translation such as targeted α-peptide receptor radiotherapy and 225 Ac-PSMA-617 for treatment of prostate cancer, innovative therapeutic models evaluating new targets, and combination therapies. Targeted α-therapy is one of the most promising fields in novel targeted cancer therapy, with several early- and late-stage clinical trials for neuroendocrine tumors and metastatic prostate cancer already in progress, along with significant interest and investment in additional early-phase studies. Together, these studies will help us understand the short- and long-term toxicity of targeted α-therapy and potentially identify suitable therapeutic combination partners., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Objectives: Prostate-specific membrane antigen (PSMA) PET/computed tomography (CT) is a novel imaging tool with an evolving role in the management of prostate cancer. This study aims to retrospectively evaluate the impact of 68Ga-PSMA PET/CT on prostate cancer staging and definitive radiation therapy planning., Methods: Between April 2015 and June 2020, 366 men with prostate cancer were evaluated with 68Ga-PSMA PET/CT. Of these, 108 patients had PSMA PET/CT before radiation therapy. Radiation was given as primary treatment in 58 (54%) and as salvage radiation therapy for biochemical recurrence after primary surgery in 50 (46%) patients, respectively. Patient and disease characteristics were analyzed, and impact of PSMA PET/CT on disease staging and radiotherapy planning was evaluated in comparison to conventional imaging., Results: Median age at presentation was 69 years, and median prostate-specific antigen was 18 ng/mL (3.6-400) for primary and 0.4 ng/mL (0.1-4.6) for salvage radiation, respectively. The combined change of disease stage rate was 36% (39/108) with 45% (26/58) in the subgroup of primary radiation and 26% (13/50) in the patients intended for salvage radiation. Upstaging was found in 24 (22%) and downstaging in 15 (14%) patients. Radiation planning was changed based on PSMA PET/CT in 34 (31%) patients, including 7 (6.4%) patients in which stereotactic body radiotherapy (SBRT) was added to oligometastatic sites. The radiation field was extended to include pelvic lymph node involvement in 21 patients., Conclusions: 68Ga-PSMA PET/CT changed the prostate cancer stage in around one-third of men. PSMA PET/CT significantly impacted radiation planning. Further prospective studies are still required., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Our purpose was to determine the relationship between serum prostate-specific antigen (PSA) level categories (<5, 5-10, 10-20, and >20 ng/mL) and the incidence of bone metastases detected by total-body 68 Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT and to assess if expanding the 68 Ga-PSMA-11 PET/CT imaging field to include the vertex and lower extremities (total-body acquisition) affects bone metastasis detection rates and patient management. Methods: This was a retrospective analysis of 388 prostate cancer patients enrolled in 5 prospective studies (NCT02940262, NCT03368547, NCT03042312, NCT04050215, and NCT03515577). All underwent 68 Ga-PSMA-11 PET/CT scans acquired from vertex to toes for primary staging ( n = 93/388, 24%), biochemical recurrence (BCR) localization ( n = 225/388, 58%), or restaging metastatic disease (M1) before or during systemic therapy ( n = 70/388, 18%) between September 2017 and May 2018. Results: In total, 321 of 388 patients (83%) had a positive 68 Ga-PSMA-11 study. PSMA-positive bone lesions were found in 105 of 388 (27%) patients, with an incidence that was positively associated with serum PSA level (<10 ng/mL, 21%; 10-20 ng/mL, 41%; ≥20 ng/mL, 41%; P < 0.001). This association was maintained for all 3 indications: initial staging, BCR, and restaging M1. Bone metastases occurred most frequently in restaging M1, followed by BCR and initial staging. Bone metastasis incidence was not significantly associated with National Comprehensive Cancer Network risk score ( P = 0.22). The average number of PSMA-positive regions also increased with serum PSA level ( P < 0.001). Eighteen of 388 (5%) and 18 of 388 (5%) had lesions above the superior orbital ridge and below the proximal third of the femur, respectively. There was only 1 of 388 patients (0.26%) in whom the total-body PET acquisition had an impact on management. Conclusion: Bone metastases as assessed with 68 Ga-PSMA-11 PET/CT are prevalent even in patients with low serum PSA levels. Therefore, current guidelines for bone assessments in prostate cancer patients should be revisited because 68 Ga-PSMA-11 PET/CT may provide additional information for accurate bone staging at low serum PSA levels. Including the total body (from vertex to toes) in 68 Ga-PSMA-11 PET/CT imaging revealed additional bone lesions in 6% of patients, but without significantly affecting patient management., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

According to SEER Cancer Statistics Review there are around 165,000 new prostate cancer cases estimated in 2018 accounting for 9.5% of all newly diagnosed cancers. Accurate staging of primary prostate cancer is important for therapy selection (local vs systemic). Recent developments in molecular imaging may significantly impact staging procedures and management. Accordingly, this article addresses the current clinical standard, discusses the areas of unmet clinical need for imaging and then summarizes the most commonlyused molecular imaging probes. Finally, the authors dare an outlook to the short-term future role of molecular imaging in primary staging of prostate cancer., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Our purpose was to determine the relationship between serum prostate-specific antigen (PSA) level categories (20 ng/mL) and the incidence of bone metastases detected by total-body 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT and to assess if expanding the 68Ga-PSMA-11 PET/CT imaging field to include the vertex and lower extremities (total-body acquisition) affects bone metastasis detection rates and patient management. Methods: This was a retrospective analysis of 388 prostate cancer patients enrolled in 5 prospective studies (NCT02940262, NCT03368547, NCT03042312, NCT04050215, and NCT03515577). All underwent 68Ga-PSMA-11 PET/CT scans acquired from vertex to toes for primary staging (n = 93/388, 24%), biochemical recurrence (BCR) localization (n = 225/388, 58%), or restaging metastatic disease (M1) before or during systemic therapy (n = 70/388, 18%) between September 2017 and May 2018. Results: In total, 321 of 388 patients (83%) had a positive 68Ga-PSMA-11 study. PSMA-positive bone lesions were found in 105 of 388 (27%) patients, with an incidence that was positively associated with serum PSA level (