Prostate-specific Membrane Antigen Research Articles

Extraordinary therapeutic effect of PSMA radioligand therapy in treatment-refractory progressive metastatic prostate cancer with the transketolase inhibitor benfo-oxythiamine as a radiosensitizer—A case report

Herein we report, for the first time, the therapeutic response of a prostate cancer patient with the thiamine antagonist benfo-oxythiamine (B-OT) added to prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (PRLT). The patient was initially diagnosed as pT3b pN0 (0/7) M0 L0 V0 R0 G3, Gleason score 5 + 5 = 10, with an initial prostate-specific antigen (PSA) level of 4.05 ng/ml. Shortly after radical prostatectomy, 68Ga-PSMA positron emission tomography/computed tomography (PET/CT) revealed PSMA-positive lymph node metastases. Despite treatment with androgen deprivation therapy, external beam radiation therapy, palliative chemotherapy, and five cycles of PRLT (177Lu-PRLT or TANDEM-PRLT, respectively), the patient experienced progression in PSA levels as well as in PSMA PET/CT. Due to the intense PSMA expression, 177Lu-PRLT with 177Lu-PSMA-I&T was resumed for another 4 cycles (cycles 6th to 9th) and the patient was additionally treated with the thiamine antagonist benfo-oxythiamine. It was hypothesized that B-OT acts as a radiosensitizer by interfering with the repair of damaged DNA. B-OT-PRLT was well-tolerated and no substantial changes in laboratory results were observed. Additionally, the patient reported significant improvement in clinical symptoms. Post-treatment 177Lu-PSMA single-photon computed tomography (SPECT)/CT after the 7th cycle (and after 2 cycles of B-OT-PRLT) revealed regression of metastases compared to the post-treatment SPECT/CT after the 6th cycle. Before the 8th cycle, PSMA PET/CT showed a mixed response following prior uncontrollable cancer progression. Moreover, the PSA level showed a significant decline after one cycle of B-OT-PRLT. Although the patient had experienced massive progression before the first cycle of B-OT-PRLT, he survived for an additional 12 months. This case supports the hypothesis that B-OT-PRLT could overcome radiation resistance in prostate cancer patients who do not initially respond to 177Lu- or 225Ac-PRLT.

The first experience of multi-modal in vivo PET/SPECT/CT and MRI imaging of laboratory mice with melanoma B16F10 (short message)

Background. For in vivo determination of size and metabolic characteristics of model tumors in laboratory animals, it is recommended to use imaging methods: positron emission tomography (PET), single-photon emission computed tomography (SPECT), computed tomography (CT) and magnetic resonance imaging (MRI). Due to the limited availability of hybrid scanners, it is necessary to investigate the feasibility of obtaining tomograms on separate devices with subsequent geometric comparison of images.Aim. To investigate the feasibility of multimodal imaging of mice with subcutaneous melanoma B16F10.Materials and methods. PET, SPECT and CT were performed using a preclinical VECTor 6 tomograph (MILabs, the Netherlands), MRI was performed using a preclinical nanoScan® 3T tomograph (Mediso, Hungary). The following modality combinations were studied: MRI and PET / CT with 18F-fluorodeoxyglucose; MRI and PET / CT with 18F-boronphenylalanine; MRI and PET / SPECT / CT with 18F-fluoroethyltyrosine (18F-FET) and 177lutetium – prostate-specific membrane antigen (177Lu-PSMA). Mice were immobilized in a custom-made device during scanning and during movement between tomographs. PET and MRI, SPECT and MRI images were fused in the program InterView FUSION 3.09.008.0000 through an intermediate stage of fusion with CT.Results. Multimodal PET / CT / MRI and PET / SPECT / CT / MRI images of tumor-bearing mice were obtained for the first time in Russia. PET / MRI data confirmed development of the tumor from 6 × 4 × 4 mm in size. PET / SPECT / CT / MRI enabled to image visceral organs with high accumulation of radionuclide tracers: pancreas with 18F-FET (standardized uptake value 2.6) and kidneys with 177Lu-PSMA (standardized uptake value 4.4), while the obtained images of organs did not merge and did not overlap.Conclusion. Multimodal imaging enables the selection of experimental animals with tumors of specific size and metabolic activity for the study of new radiopharmaceuticals, including those with vector delivery.

Outstanding increase in tumor-to-background ratio over time allows tumor localization by [89Zr]Zr-PSMA-617 PET/CT in early biochemical recurrence of prostate cancer

BackgroundPositron emission tomography/computed tomography (PET/CT) using prostate-specific membrane antigen (PSMA)-targeted radiotracers labeled with zirconium-89 (89Zr; half-life ~ 78.41 h) showed promise in localizing biochemical recurrence of prostate cancer (BCR) in pilot studies.MethodsRetrospective analysis of 38 consecutive men with BCR (median [minimum–maximum] prostate-specific antigen 0.52 (0.12–2.50 ng/mL) undergoing [89Zr]Zr-PSMA-617 PET/CT post-negative [68Ga]Ga-PSMA-11 PET/CT. PET/CT acquisition 1-h, 24-h, and 48-h post-injection of a median (minimum–maximum) [89Zr]Zr-PSMA-617 tracer activity of 123 (84–166) MBq.Results[89Zr]Zr-PSMA-617 PET/CT detected altogether 57 lesions: 18 local recurrences, 33 lymph node metastases, 6 bone metastases in 30/38 men with BCR (78%) and prior negative conventional PSMA PET/CT. Lesion uptake significantly increased from 1-h to 24-h and, in a majority of cases, from 24-h to 48-h. Tumor-to-background ratios significantly increased over time, with absolute increases of 100 or more. No side effects were noted. After [89Zr]Zr-PSMA-617 PET/CT-based treatment, prostate-specific antigen concentration decreased in all patients, becoming undetectable in a third of patients. Limitations: retrospective, single center design; infrequent histopathological and imaging verification.ConclusionThis large series provides further evidence that [89Zr]Zr-PSMA-617 PET/CT is a beneficial imaging modality to localize early BCR. A remarkable increase in tumor-to-background ratio over time allows localization of tumor unidentified on conventional PSMA PET/CT.

Evaluating response to radium-223 using 68Ga-PSMA PET/CT imaging in patients with metastatic castration-resistant prostate cancer.

Conventional imaging techniques and prostate-specific antigen (PSA) values are not useful to follow-up patients during Radium-223 treatment. The study aimed to evaluate the predictive value of prostate-specific membrane antigen PSMA PET/CT-based response in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving Radium-223 dichloride treatment. Patients treated with radium-223, having performed two 68Ga-PSMA-11 PET/CT scans (baseline 1month before treatment initiation and follow-up 2weeks after the third cycle), were retrospectively evaluated. Visual and quantitative PET image analyses were performed, and patients were dichotomized into progressive (PD) and non-PD according to Response Evaluation Criteria in PSMA‑imaging (RECIP1.0) and PSMA-PET Progression criteria (PPP). The primary endpoint was overall survival (OS). Cohen's Kappa (κ) was used to test the agreement between the two criteria. The Cox regression hazard model and Kaplan-Meier method were used for survival analyses. Twenty-eight mCRPC patients were evaluated. Sixteen (43%) and 18 (64%) patients had PD according to RECIP1.0 and PPP, respectively; κ = 0.85 (95% CI 0.65-1.00). After a median follow-up of 16months (interquartile IQR 9-33), 20 (71%) patients died. Patients with PSMA PD showed a higher risk of death than non-PD according to RECIP1.0 (HR = 2.9; 95% CI 1.14-7.46; p = 0.029) and PPP (HR = 2.8; 95% CI 1.04-7.64; p = 0.042). For both criteria, the median OS was shorter for PD than non-PD (37 vs. 12months, Log-rank; p < 0.05). The C-index for RECIP1.0 and PPP were almost equal (0.66 and 0.63; respectively). This study demonstrated that PSMA-PET/CT imaging is valuable for monitoring radium-223 treatment. Both PSMA PET/CT response criteria (RECIP1.0 and PPP) perform similarly predicting OS at follow-up after three cycles of radium-223. These findings urge further validation in prospective trials.

Best Patient Care Practices for Administering PSMA-Targeted Radiopharmaceutical Therapy.

Optimal patient management protocols for metastatic castration-resistant prostate cancer (mCRPC) are poorly defined and even further complexified with new therapy approvals, such as radiopharmaceuticals. The prostate-specific membrane antigen (PSMA)-targeted agent 177Lu vipivotide tetraxetan ([177Lu]Lu-PSMA-617), approved after the phase III VISION study, presents physicians with additional aspects of patient management, including specific adverse event (AE) monitoring and management, as well as radiation safety. Drawing on our experience as VISION study investigators, here we provide guidance on best practices for delivering PSMA-targeted radiopharmaceutical therapy (RPT) to patients with mCRPC. After a comprehensive review of published evidence and guidelines on RPT management in prostate cancer, we identified educational gaps in managing the radiation safety and AEs associated with [177Lu]Lu-PSMA-617. Our results showed that providing sufficient education on AEs (e.g., fatigue and dry mouth) and radiation safety principles is key to effective delivery and management of patient expectations. Patient counseling by health care professionals, across disciplines, is a cornerstone of optimal patient management during PSMA-targeted RPT. Multidisciplinary collaboration is crucial, and physicians must adhere to radiation safety protocols and counsel patients on radiation safety considerations. Treatment with [177Lu]Lu-PSMA-617 is generally well tolerated; however, additional interventions may be required, such as dosing modification, medications, or transfusions. Urinary incontinence can be challenging in the context of radiation safety. Multidisciplinary collaboration between medical oncologists and nuclear medicine teams ensures that patients are monitored and managed safely and efficiently. In clinical practice, the benefit-to-risk ratio should always be evaluated on a case-by-case basis.

Medicinal (Radio)Chemistry: Building Radiopharmaceuticals for the Future.

Radiopharmaceuticals are increasingly playing a leading role in diagnosing, monitoring, and treating disease. In comparison with conventional pharmaceuticals, the development of radiopharmaceuticals does follow the principles of medicinal chemistry in the context of imaging-altered physiological processes. The design of a novel radiopharmaceutical has several steps similar to conventional drug discovery and some particularity. In the present work, we revisited the insights of medicinal chemistry in the current radiopharmaceutical development giving examples in oncology, neurology, and cardiology. In this regard, we overviewed the literature on radiopharmaceutical development to study overexpressed targets such as prostate-specific membrane antigen and fibroblast activation protein in cancer; β-amyloid plaques and tau protein in brain disorders; and angiotensin II type 1 receptor in cardiac disease. The work addresses concepts in the field of radiopharmacy with a special focus on the potential use of radiopharmaceuticals for nuclear imaging and theranostics.

Prostate-Specific Membrane Antigen-Positron Emission Tomography-Guided Radiomics and Machine Learning in Prostate Carcinoma

Positron emission tomography (PET) using radiolabeled prostate-specific membrane antigen targeting PET-imaging agents has been increasingly used over the past decade for imaging and directing prostate carcinoma treatment. Here, we summarize the available literature data on radiomics and machine learning using these imaging agents in prostate carcinoma. Gleason scores derived from biopsy and after resection are discordant in a large number of prostate carcinoma patients. Available studies suggest that radiomics and machine learning applied to PSMA-radioligand avid primary prostate carcinoma might be better performing than biopsy-based Gleason-scoring and could serve as an alternative for non-invasive GS characterization. Furthermore, it may allow for the prediction of biochemical recurrence with a net benefit for clinical utilization. Machine learning based on PET/CT radiomics features was also shown to be able to differentiate benign from malignant increased tracer uptake on PSMA-targeting radioligand PET/CT examinations, thus paving the way for a fully automated image reading in nuclear medicine. As for prediction to treatment outcome following 177Lu-PSMA therapy and overall survival, a limited number of studies have reported promising results on radiomics and machine learning applied to PSMA-targeting radioligand PET/CT images for this purpose. Its added value to clinical parameters warrants further exploration in larger datasets of patients.

Prediction of lesion-based treatment response after two cycles of Lu-177 PSMA treatment in metastatic castration-resistant prostate cancer using machine learning.

Introduction Lutetium-177 (Lu-177) prostate specific membrane antigen (PSMA) therapy is a radionuclide treatment that prolongs overall survival in metastatic castration-resistant prostate cancer (MCRPC). We aimed to predict lesion-based treatment response after Lu-177 PSMA treatment using machine learning with texture analysis data obtained from pretreatment Gallium-68 (Ga-68) PSMA PET/CT. Methods Eighty-three progressed, and 91 nonprogressed malignant foci on pretreatment Ga-68 PSMA PET/CT of 9 patients were used for analysis. Malignant foci with at least a 30% increase in Ga-68 PSMA uptake after two cycles of treatment were considered progressed lesions. All other changes in Ga-68 PSMA uptake of the lesions were considered nonprogressed lesions. The classifiers tried to predict progressed lesions. Results Logistic regression, Naive Bayes, and k-nearest neighbors' AUC values in detecting progressed lesions in the training group were 0.956, 0.942, and 0.950, respectively, and their accuracy was 87%, 85%, and 89%, respectively. The AUC values of the classifiers in the testing group were 0.937, 0.954, and 0.867, respectively, and their accuracy was 85%, 88%, and 79%, respectively. Conclusion Using machine learning with texture analysis data obtained from pretreatment Ga-68 PSMA PET/CT in MCRPC predicted lesion-based treatment response after two cycles of Lu-177 PSMA treatment.

Assessing ChatGPT's summarization of 68Ga PSMA PET/CT reports for patients.

ChatGPT has recently been the subject of many studies, and its responses to medical questions have been successful. We examined ChatGPT-4's evaluation of structured 68Ga prostate-specific membrane antigen (PSMA) PET/CT reports of newly diagnosed prostate cancer patients. 68Ga PSMA PET/CT reports of 164 patients were entered to ChatGPT-4. ChatGPT-4 was asked to respond the following questions according to the PET/CT reports: 1-Has the cancer in the prostate extended to organs adjacent to the prostate? 2-Has the cancer in the prostate spread to neighboring lymph nodes? 3-Has the cancer in the prostate spread to lymph nodes in distant areas? 4-Has the cancer in the prostate spread to the bones? 5-Has the cancer in the prostate spread to other organs? ChatGPT-4's responses were scored on a Likert-type scale for clarity and accuracy. The mean scores for clarity were 4.93 ± 0.32, 4.95 ± 0.25, 4.96 ± 0.19, 4.99 ± 0.11, and 4.96 ± 0.30, respectively. The mean scores for accuracy were 4.87 ∓ 0.61, 4.87 ∓ 0.62, 4.79 ± 0.83, 4.96 ± 0.25, and 4.93 ± 0.45, respectively. Patients with distant lymphatic metastases had a lower mean accuracy score than those without (4.28 ± 1.45 vs. 4.94 ± 0.39; p < 0.001). ChatGPT-4's responses in 13 patients (8%) had the potential for harmful information. ChatGPT-4 successfully interprets structured 68Ga PSMA PET/CT reports of reports of newly diagnosed prostate cancer patients. However, it is unlikely that ChatGPT-4 evaluations will replace physicians' evaluations today, especially since it can produce fabricated information.

Head-to-head comparison of GA-68 PSMA PET/CT and multiparametric MRI findings with postoperative results in preoperative locoregional staging and localization of prostate cancer.

Accurate staging of prostate cancer (PCa) is essential for determining the appropriate treatment and predicting outcomes. This study is comparing the effectiveness of Gallium-68 Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography (Ga-68 PSMA PET/CT) and multiparametric MRI (mpMRI) in preoperative locoregional staging and localizing PCa. A retrospective analysis was conducted on 78 patients who underwent both mpMRI and Ga-68 PSMA PET/CT scans before surgery. The imaging was reviewed by radiologists and nuclear medicine specialists and compared with the final histopathology, which was reviewed by an experienced uropathologist. mpMRI demonstrated higher sensitivity in detecting extraprostatic extension (EPE) and bladder neck invasion (BNI) compared to Ga-68 PSMA PET/CT (83% vs. 44% and 29% vs. 17%, respectively). Conversely, Ga-68 PSMA PET/CT showed higher sensitivity in detecting seminal vesicle invasion (SVI) and lymph node metastasis (LNM) (75% vs. 55% and 50% vs. 30%, respectively). When both methods were combined, sensitivity increased in detecting both EPE and SVI. The index tumor localization in mpMRI and Ga-68 PSMA PET/CT was found to be in complete agreement with histopathological findings at 36.4% and 41.8%, respectively. When both imaging methods were combined, the agreement with histopathology in predicting index tumor localization reached 72.1%. Both mpMRI and Ga-68 PSMA PET/CT provide valuable and complementary information for tumor localization and locoregional staging. While mpMRI showed higher sensitivity in detecting EPE, Ga-68 PSMA PET/CT demonstrated superior performance in detecting LNM and SVI. The combined use of these imaging modalities enhance accuracy of index tumor localizations.

Pattern of Failure in Patients with Biochemical Recurrence After PSMA Radioguided Surgery.

Prostate-specific membrane antigen (PSMA)-targeted radioguided surgery (RGS) is evolving as a new treatment modality for patients with early biochemical recurrence of prostate cancer and disease limited to locoregional lymph nodes on PSMA-ligand PET/CT. Nevertheless, the pattern of failure (locoregional vs. systemic) after PSMA RGS remains unknown. Therefore, the aim of this retrospective analysis was to evaluate the pattern of disease using PSMA-ligand PET in patients experiencing relapse after PSMA RGS. Methods: We evaluated 100 patients with biochemical recurrence after previous PET-guided PSMA RGS who underwent PSMA-ligand PET (median prostate-specific antigen [PSA], 0.9 ng/mL; range, 0.2-14.2 ng/mL). All suspicious lesions for recurrent prostate cancer were grouped according to the molecular imaging TNM classification system. Detection rates and lesion localization were determined and stratified by PSA values and the International Society of Urological Pathology grade group. Further, lesion localization was compared before and after PSMA RGS. Results: The median time between PSMA RGS and PSMA-ligand PET for relapse was 11.4 mo (range, 5.5-25.6 mo). In total, 91 of 100 (91%) patients showed PSMA-ligand-positive findings. PSMA PET detection rates were 82.6%, 92.6%, 91.3%, and 96.3% for PSA levels of 0.2-0.49, 0.5-0.99, 1-1.99, and at least 2 ng/mL, respectively. More than half of the patients (53%; 48/91) showed local recurrence or pelvic lymph node metastases only. Extrapelvic lymph node metastases, bone metastases, and visceral metastases were present in 22% (20/91), 16% (15/91), and 9% (8/91) of the patients, respectively. With increasing International Society of Urological Pathology grade group, the percentage of patients with bone and visceral metastases increased, whereas the number of patients with only locoregional disease decreased. Conclusion: PSMA-ligand PET is a useful method to detect and localize recurrent disease in patients with biochemical failure after PSMA RGS, with more than half of the patients presenting with locoregional recurrence, offering the potential for a second local therapy (e.g., radiation therapy or repeated surgery).

Efficacy and Toxicity of [177Lu]Lu-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer: Results from the U.S. Expanded-Access Program and Comparisons with Phase 3 VISION Data.

The phase 3 VISION trial demonstrated that [177Lu]Lu-PSMA-617 prolonged progression-free survival and overall survival (OS) in prostate-specific membrane antigen [PSMA]-positive metastatic castration-resistant prostate cancer (mCRPC) patients who progressed on taxane-based chemotherapy and androgen receptor-signaling inhibitors (ARSIs). The U.S. expanded-access program (EAP; NCT04825652) was opened to provide access to [177Lu]Lu-PSMA-617 for eligible patients until regulatory approval was obtained. This study aimed to evaluate the efficacy and safety profile of [177Lu]Lu-PSMA-617 within the EAP and compare the results with those from the VISION trial. Methods: Patients enrolled in the EAP at 4 institutions in the United States with available toxicity and outcome data were included. Outcome measures included OS, a prostate-specific antigen (PSA) response rate (RR) of at least 50%, and incidences of toxicity according to Common Terminology Criteria for Adverse Events version 5.0. Differences in baseline characteristics, outcome data, and toxicity between the EAP and VISION were evaluated using t testing of proportions and survival analyses. Results: In total, 117 patients with mCRPC who received [177Lu]Lu-PSMA-617 within the EAP between May 2021 and March 2022 were eligible and included in this analysis. Patients enrolled in the EAP were more heavily pretreated with ARSI (≥2 ARSI regimens: 70% vs. 46%; P < 0.001) and had worse performance status at baseline (Eastern Cooperative Oncology Group score ≥ 2: 19% vs. 7%; P < 0.001) than VISION patients. EAP and VISION patients had similar levels of grade 3 or higher anemia (18% vs. 13%; P = 0.15), thrombocytopenia (13% vs. 8%; P = 0.13), and neutropenia (3% vs. 3%; P = 0.85) and similar PSA RRs (42% vs. 46%; P = 0.50) and OS (median: 15.1 vs. 15.3 mo; P > 0.05). Conclusion: Patients with PSMA-positive mCRPC who received [177Lu]Lu-PSMA-617 within the EAP were later in their disease trajectory than VISION patients. Patients enrolled in the EAP achieved similar PSA RRs and OS and had a safety profile similar to that of the VISION trial patients.

Diagnostic performance of simultaneous PET-magnetic resonance versus PET-computed tomography in oncology with an overview on clinical utility and referral pattern of PET-magnetic resonance: a single institutional study.

PET-magnetic resonance (PETMR) imaging is an upcoming investigative modality with a few installations in Asia and only three in India. PET-Computed tomography (PETCT) is an established diagnostic cornerstone for oncological indications but with limited resolution for small lesions due to low soft-tissue contrast and additional radiation exposure. Our primary objective was to evaluate the diagnostic performance of simultaneous PETMR and PETCT in lesion detection in oncological practice. Secondly to assess the referral pattern and study the clinical utility of PETMR in a university hospital practice. A total of 100 consecutive biopsy-proven cancer patients (breast or lung malignancy with suspected metastases) underwent 18F fluorodeoxyglucose (FDG) PETMR and PETCT for staging as a single injection, double examination protocol. Morphological lesion detection on correlative imaging/histopathology was used as the gold standard. Analysing the referral pattern, a total of 9366 patients underwent simultaneous PETMR imaging for indications in the past 5 years since installation. 18F FDG PETMR detected 100% of primary tumours in breast/lung carcinoma (Ca) patients while PETCT was positive in 96%. Overall accuracy of nodal metastases detection for PETMR and PETCT was 96 and 88%, while for distant metastases the accuracy was 100 and 93%, respectively. FDG PETMR proved more sensitive and specific than PETCT for regional nodal (P = 0.011 and P < 0.001) and distant metastases detection (P = 0.017 and P < 0.001, respectively). Analysing the general referral pattern for PETMR, the majority were oncology referrals (66.5, 33.5%) when compared to nononcological indications. About 66.24% were FDG based, followed by Ga prostate-specific membrane antigen and dodecane tetraacetic acid. The general utility of PETMR was found incremental in better delineation of small lesions especially in head, neck, liver, brain and gynaecological malignancies. In our past 5 years of PETMR practice, we found that simultaneous PETMR is a highly recommended ideal imaging technique for oncological and nononcological indications. It has excellent diagnostic performance with high sensitivity, specificity and accuracy when compared to PETCT in tumour, nodal metastases staging in specific subgroup of breast and lung malignancy patients.

Association of Free-to-Total PSA Ratio and 18F-DCFPyL Prostate-Specific Membrane Antigen PET/CT Findings in Patients with Biochemical Recurrence After Radical Prostatectomy: A Prospective Single-Center Study.

In Canada and across the globe, access to PSMA PET/CT is limited and expensive. For patients with biochemical recurrence (BCR) after treatment for prostate cancer, novel strategies are needed to better stratify patients who may or may not benefit from a PSMA PET scan. The role of the free-to-total prostate-specific antigen (PSA) ratio (FPSAR) in posttreatment prostate cancer, specifically in the PSMA PET/CT era, remains unknown. Our aim in this study was to determine the association of FPSAR in patients referred for 18F-DCFPyL PSMA PET/CT in the BCR setting and assess the correlation between FPSAR and 18F-DCFPyL PSMA PET/CT positivity (local recurrence or distant metastases). Methods: This prospective study included 137 patients who were referred for 18F-DCFPyL PSMA PET/CT and had BCR with a total PSA of less than 1 ng/mL after radical prostatectomy (RP) (including adjuvant or salvage radiotherapy). Blood samples were collected on the day of 18F-DCFPyL PSMA PET/CT. FPSAR was categorized as less than 0.10 or as 0.10 or more. A positive 18F-DCFPyL PSMA PET/CT scan was defined by a PROMISE classification lesion score of 2 or 3, irrespective of the site of increased tracer uptake (e.g., prostate, pelvic nodes, bone, or viscera). Results: Overall, 137 blood samples of patients with BCR after RP were analyzed to calculate FPSAR. The median age at 18F-DCFPyL PSMA PET/CT was 68.6 y (interquartile range, 63.0-72.4 y), and the median PSA at 18F-DCFPyL PSMA PET/CT was 0.3 ng/mL (interquartile range, 0.3-0.6 ng/mL). Eighty-six patients (62.8%) had an FPSAR of less than 0.10, whereas 51 patients (37.2%) had an FPSAR of 10 or more. An FPSAR of 10 or more was identified as an independent predictor of a positive 18F-DCFPyL PSMA PET/CT scan, with an odds ratio of 6.99 (95% CI, 2.96-16.51; P < 0.001). Conclusion: An FPSAR of 10 or more after RP independently correlated with increased odds of a positive 18F-DCFPyL PSMA PET/CT scan among BCR post-RP patients. These findings may offer an inexpensive method by which to triage access to 18F-DCFPyL PSMA PET/CT in jurisdictions where availability is not replete.

PSMA and Sigma-1 receptor dual-targeted peptide mediates superior radionuclide imaging and therapy of prostate cancer

Radionuclide therapy, in particular peptide receptor radionuclide therapy (PRRT), has emerged as a valuable means to combat malignant tumors. The specific affinity of ACUPA peptide toward prostate-specific membrane antigen (PSMA) renders the successful development of PRRT for prostate cancer. The clinical outcome of PRRT is, however, generally challenged by moderate tumor uptake and off-target toxicity. Here, we report on a novel design of Sigma-1 receptor and PSMA dual-receptor targeted peptide (S1R/PSMA-P) for superior radionuclide imaging and therapy of prostate cancer. S1R/PSMA-P was acquired with good purity and could efficiently be labeled with 177Lu to yield 177Lu-S1R/PSMA-P with high specific activity and radiostability. Interestingly, 177Lu-S1R/PSMA-P revealed greatly enhanced affinity to LNCaP cells over single-targeted control 177Lu-PSMA-617. The single photon emission computed tomography (SPECT) imaging demonstrated exceptional uptake and retention of 177Lu-S1R/PSMA-P in LNCaP tumor, affording about 2-fold better tumor accumulation while largely reduced uptake by most normal tissues compared to 177Lu-PSMA-617. The selective uptake in LNCaP tumor was also visualized by positron emission tomography (PET) with 68Ga-S1R/PSMA-P. In accordance, a single and low dosage of 177Lu-S1R/PSMA-P at 11.1 MBq effectively suppressed tumor growth without causing apparent side effects. This dual-targeting strategy presents an appealing radionuclide therapy for malignant tumors.

A Novel Targeted Microtubules Transformable Nanopeptide System Yields Strong Anti-Prostate Cancer Effects by Suppressing Nuclear Translocation of Androgen Receptors.

The extended use of androgen deprivation therapy (ADT) may often lead to the progression from castration-sensitive prostate cancer (CSPC) to castration-resistant prostate cancer (CRPC) in prostate cancer. To address this, it is essential to inhibit the nuclear translocation of the androgen receptor (AR) as part of an effective disease-modifying strategy. Microtubules play a central role in facilitating AR nuclear translocation, highlighting their importance as a therapeutic target. In this regard, a designated as the targeted microtubules transformable nanopeptide system (MTN) is developed. This system is designed to disrupt microtubule structure and function through dual-targeting of prostate-specific membrane antigen (PSMA) and β-tubulin. Initially, MTN targets prostate cells via PSMA and then specifically binds to β-tubulin within microtubules, leading to the formation of nanofibers. These nanofibers subsequently induce the polymerization of microtubules, thereby disrupting AR transport. Notably, MTN exhibits efficient and prolonged suppression of prostate cancer across the spectrum from CSPC to CRPC, with a highly favorable safety profile in normal cells. These findings highlight the potential of MTN as a novel and promising approach for comprehensive prostate cancer therapy throughout its entire progression.

Imaging in Renal Cell Carcinoma Detection.

Imaging in renal cell carcinoma (RCC) is a constantly evolving landscape. The incidence of RCC has been rising over the years with the improvement in image quality and sensitivity in imaging modalities resulting in "incidentalomas" being detected. We aim to explore the latest advances in imaging for RCC. A literature search was conducted using Medline and Google Scholar, up to May 2024. For each subsection of the manuscript, a separate search was performed using a combination of the following key terms "renal cell carcinoma", "renal mass", "ultrasound", "computed tomography", "magnetic resonance imaging", "18F-Fluorodeoxyglucose PET/CT", "prostate-specific membrane antigen PET/CT", "technetium-99m sestamibi SPECT/CT", "carbonic anhydrase IX", "girentuximab", and "radiomics". Studies that were not in English were excluded. The reference lists of selected manuscripts were checked manually for eligible articles. The main imaging modalities for RCC currently are ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI). Contrast-enhanced US (CEUS) has emerged as an alternative to CT or MRI for the characterisation of renal masses. Furthermore, there has been significant research in molecular imaging in recent years, including FDG PET, PSMA PET/CT, 99mTc-Sestamibi, and anti-carbonic anhydrase IX monoclonal antibodies/peptides. Radiomics and the use of AI in radiology is a growing area of interest. There will be significant change in the field of imaging in RCC as molecular imaging becomes increasingly popular, which reflects a shift in management to a more conservative approach, especially for small renal masses (SRMs). There is the hope that the improvement in imaging will result in less unnecessary invasive surgeries or biopsies being performed for benign or indolent renal lesions.

Whole‐body MRI for staging prostate cancer: a narrative review

ObjectiveTo present a narrative review regarding the diagnostic accuracy of whole‐body magnetic resonance imaging (WBMRI) in staging patients with high‐risk prostate cancer (HRPCa) and compare it to established imaging modalities.MethodsA narrative review was carried out using PubMed using the following keywords: ‘whole body’, ‘magnetic resonance imaging’, ‘MRI’, ‘prostate cancer’, ‘risk stratification’, and ‘staging’. Articles that evaluated WBMRI as the imaging modality to stage patients with HRPCa were included, while studies that solely assessed for biochemical recurrence or metastatic disease progression were excluded.ResultsIn the evaluation of lymphatic metastases, WBMRI has demonstrated a comparable, if not improved, sensitivity and specificity compared to conventional imaging of computed tomography (CT). Furthermore, WBMRI demonstrates improved sensitivity and specificity in detecting bone metastases compared to bone scintigraphy (BS). However, with advent of prostate‐specific membrane antigen (PSMA) radioligands for positron emission tomography (PET), the diagnostic performance of WBMRI to detect metastatic disease appears inferior.ConclusionsThe diagnostic capabilities of WBMRI exceed that of conventional imaging of CT and BS in detecting metastatic disease in patients with HRPCa. However, WBMRI does not perform as well as PSMA PET/CT. Further study on cost comparisons between WBMRI and PSMA PET/CT are needed, as well as evaluations of combined PSMA PET/MRI are needed.

Synthesis and Evaluation of 99mTc-Labeled DPro-Gly-Containing Tracers Targeting PSMA.

The specific expression of prostate-specific membrane antigen (PSMA) makes it an ideal target for the diagnosis and treatment of prostate cancer. Currently, many 99mTc-labeled PSMA-targeted tracers have been developed. However, the high renal uptake of these 99mTc-labeled tracers is a common problem that limits their clinical application. In this work, the ligand (EUKPG) using DPro-Gly as the linker was synthesized and three 99mTc-labeled complexes ([99mTc]Tc-EUKPG-EDDA, [99mTc]Tc-EUKPG-TPPTS, [99mTc]Tc-EUKPG-TPPMS) with different coligands were prepared and evaluated. Among them, [99mTc]Tc-EUKPG-EDDA showed the most favorable pharmacokinetic properties, with significantly reduced uptake in the kidney (14.04 ± 0.23% ID/g), rapid clearance and low uptake in nontarget organs, thus making it to exhibit high tumor-to-background ratios (tumor/blood: 7.47, tumor/muscle: 12.65). Affinity studies have shown that it has high specificity for PSMA both in vivo and in vitro. Therefore, [99mTc]Tc-EUKPG-EDDA has great potential as a promising molecular tracer to target PSMA for tumor imaging.

Personalized dosimetry assessment of [177Lu]Lu-PSMA-617 radioligand therapy in the management of metastatic castration-resistant prostate cancer

Introduction Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is revolutionizing the treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) patients. This study aimed to establish patient-specific radiation dosimetry for [177Lu]Lu-PSMA-617 RLT in Iranian patients with mCRPC. Method Twelve biopsy-proven prostate cancer patients (aged 68.73 ± 5.26 yr) underwent 6.62 ± 0.36 GBq [177Lu]Lu-PSMA-617 RLT. Post-therapy whole-body planar scans were acquired approximately at 4, 48, and 72 h post-administration, alongside a single SPECT/CT around 48 h using Siemens Symbia T2 to obtain cumulated activity. An imaging protocol and dosimetry approach were designed to balance between time efficacy and accuracy in post-therapeutic dosimetry. Using accurate activity calibration, S-values were calculated by importing SPECT/CT images as the source/geometry into the Geant4 application for the tomographic emission (GATE) Monte Carlo (MC) toolkit. The Medical Internal Radiation Dose (MIRD) scheme was followed for subsequent absorbed dose (AD) calculations in organs at risk (OAR) and tumoral lesions using the dose actor and accumulated activities for precise dose estimations. Results Using the MC approach, the mean ADs to the liver, spleen, right and left kidneys, and tumor lesions were 0.11 ± 0.04 Gy/GBq, 0.08 ± 0.03 Gy/GBq, 0.34 ± 0.09 Gy/GBq, 0.34 ± 0.10 Gy/GBq, and 0.83 ± 0.54 Gy/GBq, respectively. Notably, tumoral lesions demonstrated significantly higher ADs, indicating enhanced uptake of radiopharmaceuticals by malignant cells. Conclusions This study indicates that the ADs of OARs and tumoral lesions from [177Lu]Lu-PSMA-617 RLT in patients with mCRPC are consistent with existing literature. The dosimetry findings suggest that increasing the administered activity of [177Lu]Lu-PSMA-617 RLT is feasible and does not pose a significant risk of adverse effects on OARs, as supported by our data. However, to validate the safety and efficacy of higher doses, further clinical follow-up studies are recommended.