Prostate-specific Membrane Antigen Positron Emission Tomography Research Articles

Predictors of Bone Metastases at 68Ga-PSMA-11 PET/CT in Hormone-Sensitive Prostate Cancer (HSPC) Patients with Early Biochemical Recurrence or Persistence.

Prostate-specific-membrane-antigen/positron-emission-tomography (PSMA-PET) can accurately detect disease localizations in prostate cancer (PCa) patients with early biochemical recurrence/persistence (BCR/BCP), allowing for more personalized image-guided treatments in oligometastatic patients with major impact in the case of bone metastases (BM). Therefore, this study aimed to identify predictors of BM at PSMA-PET in early-BCR/BCP hormone-sensitive PCa (HSPC) patients, previously treated with radical intent (radiotherapy or radical prostatectomy ± salvage-radiotherapy (SRT)). A retrospective analysis was performed on 443 68Ga-PSMA-11-PET/CT scans. The cohort median PSA at PET-scan was 0.60 (IQR: 0.38–1.04) ng/mL. PSMA-PET detection rate was 42.0% (186/443), and distant lesions (M1a/b/c) were found in 17.6% (78/443) of cases. BM (M1b) were present in 9.9% (44/443) of cases, with 70.5% (31/44) showing oligometastatic spread (≤3 PSMA-positive lesions). In the multivariate binary logistic regression model (accuracy: 71.2%, Nagelkerke-R2: 13%), T stage ≥ 3a (OR: 2.52; 95% CI: 1.13–5.60; p = 0.024), clinical setting (previous SRT vs. first-time BCR OR: 2.90; 95% CI: 1.32–6.35; p = 0.008), and PSAdt (OR: 0.93; 95% CI: 0.88–0.99; p = 0.026) were proven to be significant predictors of bone metastases, with a 7% risk increment for each single-unit decrement of PSAdt. These predictors could be used to further refine the indication for PSMA-PET in early BCR/BCP HSPC patients, leading to higher detection rates of bone disease and more personalized treatments.

Feasibility and Optimal Time Point of [68Ga]Gallium-labeled Prostate-specific Membrane Antigen Ligand Positron Emission Tomography Imaging in Patients Undergoing Cytoreductive Surgery After Systemic Therapy for Primary Oligometastatic Prostate Cancer: Implications for Patient Selection and Extent of Surgery

BackgroundProstate-specific membrane antigen (PSMA) targeted molecular imaging using positron emission tomography (PET) has significantly improved the diagnosis and treatment of prostate cancer (PCA). ObjectiveTo assess the feasibility and compare the diagnostic accuracy of [68Ga]Ga-PSMA-11 PET images taken at baseline, before the initiation of systemic treatment and preoperative images, using histopathology after cytoreductive surgery as reference. Design, setting, and participantsWe identified 20 patients in our prospectively maintained database with primary oligometastatic PCA who underwent cytoreductive radical prostatectomy and superextended pelvic lymph node dissection after systemic therapy, who had baseline and preoperative [68Ga]Ga-PSMA-11 PET imaging available. Outcome measurements and statistical analysisWe performed a region-based analysis to determine the diagnostic accuracy of imaging, using pathology as a reference. Regions were predefined as prostate, internal iliac left/right, obturator left/right, external iliac left/right, common iliac left/right, and presacral. Results and limitationsSensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and diagnostic effectiveness were, respectively, 95.65%, 78.22%, 98.39%, 57.89%, and 83.00% for baseline [68Ga]Ga-PSMA-11 PET, compared to 56.52%, 98.05%, 88.30%, 89.66%, and 88.50% for preoperative [68Ga]Ga-PSMA-11 PET. On a receiver operating characteristic analysis, the diagnostic accuracy of baseline [68Ga]Ga-PSMA-11 PET with an area under the curve (AUC) of 0.87 (95% confidence interval [CI] 0.83–0.92) was significantly better than that of preoperative [68Ga]Ga-PSMA-11 PET after systemic therapy with an AUC of 0.77 (95% CI 0.70–0.85, p = 0.01). ConclusionsBaseline imaging, [68Ga]Ga-PSMA-11 PET has significantly better diagnostic accuracy, sensitivity, and NPV than images obtained preoperatively, in systemically pretreated patients. If a patient is suitable for local treatment and complete resection of the residual tumor is intended, [68Ga]Ga-PSMA-11 PET images taken prior to systemic therapy are significantly more accurate in selecting the relevant lymph nodes for resection. Patient summaryWe found that prostate-specific membrane antigen positron emission tomography (PSMA-PET) imaging used early, before hormonal therapy or chemotherapy, provides more accurate information about the spread of the disease, than if used immediately before surgery but after hormonal therapy or chemotherapy. Early use of PSMA-PET has the potential to improve therapy also at later stages of the disease.

MP51-13 FLUORINE-18 (18F) PROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA) POSITRON EMISSION TOMOGRAPHY (PET) AND THE DIAGNOSIS AND STAGING OF PRIMARY PROSTATE CANCER (PCA)

MP51-13 FLUORINE-18 (18F) PROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA) POSITRON EMISSION TOMOGRAPHY (PET) AND THE DIAGNOSIS AND STAGING OF PRIMARY PROSTATE CANCER (PCA)

An Explorative Study of the Incidental High Renal Excretion of [18F]PSMA-1007 for Prostate Cancer PET/CT Imaging.

Simple SummaryProstate cancer is one of the most dominant cancers in the Western world. In recent years, the use of positron emission tomography (PET) targeting prostate-specific membrane antigen (PSMA) to image prostate cancer allows accurate diagnosis and staging. Compared to the recently registered PET tracers [68Ga]Ga-PSMA-11 and [18F]DCFPyL, [18F]PSMA-1007 is predominantly excreted by the hepatobiliary tract, resulting in much lower urinary uptake. This allows for an improved evaluation of the pelvic area. However, on some occasions, clinicians do observe high excretion of [18F]PSMA-1007 by the renal system. Yet, this sudden differential metabolism of [18F]PSMA-1007 remains poorly understood. In this retrospective study, we aimed to elucidate the incidental high urinary uptake of [18F]PSMA-1007 by assessing the individual patient characteristics, scan (data) and peptide batches.Positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) allows for accurate diagnosis and staging of prostate cancer (PCa). Compared to other PSMA PET tracers available, [18F]PSMA-1007 is predominantly excreted via the hepatobiliary tract resulting in low renal excretion which improves evaluation of the pelvic area. However, some patients do show high urinary uptake of [18F]PSMA-1007. The present study aimed to investigate this sudden high urinary uptake of [18F]PSMA-1007 by evaluating [18F]PSMA-1007 PET scans from PCa patients. In this single-center retrospective study, patients that underwent [18F]PSMA-1007 PET imaging between July 2018 and January 2021 were included. Data regarding the individual patient characteristics, scan acquisition and batch production were analyzed. To determine the urinary excretion of [18F]PSMA-1007, a region of interest was drawn in the bladder, and standardized uptake values (SUVs) were calculated and compared to SUVs in the prostate. An SUVmax of >10 was considered high urinary excretion, an SUVmax 7.5–10 intermediate and an SUVmax < 7.5 low urinary excretion. A total of 344 patients underwent [18F]PSMA-1007 PET/CT imaging, with 37 patients receiving three or more [18F]PSMA-1007 PET/CT scans. The mean SUVmean and SUVmax of the bladder were 3.9 (SD 2.9) and 5.9 (SD 4.2), respectively. Fourteen percent of patients showed high urinary uptake of [18F]PSMA-1007. Twelve of the thirty-seven patients (32.4%) that had multiple scans showed a varying urinary uptake of [18F]PSMA-1007 per PSMA PET/CT scan. In terms of patient characteristics, risk factors, medication and blood laboratory results, no significant influencing variables were found. Nor was there a difference observed in the batch size and the mean radiochemical purity of PSMA-1007 for high- and low-excreting patients. However, the bladder volume affected the mean SUVmax in the bladder significantly, with higher SUVs in lower bladder volumes. In this study, we observed that a higher SUV in the urinary tract seemed to occur in patients with low bladder volume. A prospective study is needed to corroborate this hypothesis.

High prostate-specific membrane antigen (PSMA) positron emission tomography (PET) maximum standardized uptake value in men with PI-RADS score 4 or 5 confers a high probability of significant prostate cancer.

High prostate-specific membrane antigen (PSMA) positron emission tomography (PET) maximum standardized uptake value in men with PI-RADS score 4 or 5 confers a high probability of significant prostate cancer.

Evolving Role of Prostate-Specific Membrane Antigen-Positron Emission Tomography in Metastatic Hormone-Sensitive Prostate Cancer: More Questions than Answers?

Evolving Role of Prostate-Specific Membrane Antigen-Positron Emission Tomography in Metastatic Hormone-Sensitive Prostate Cancer: More Questions than Answers?

Utility of Biology-Guided Radiotherapy to De Novo Metastases Diagnosed During Staging of High-Risk Biopsy-Proven Prostate Cancer.

BackgroundBiology-guided radiotherapy (BgRT) uses real-time functional imaging to guide radiation therapy treatment. Positron emission tomography (PET) tracers targeting prostate-specific membrane antigen (PSMA) are superior for prostate cancer detection than conventional imaging. This study aims at describing nodal and distant metastasis distribution from prostate cancer and at determining the proportion of metastatic lesions suitable for BgRT.MethodsA single-institution patient subset from the ProPSMA trial (ID ACTRN12617000005358) was analysed. Gross tumour volumes (GTV) were delineated on the CT component of a PSMA PET/CT scan. To determine the suitability of BgRT tracking zones, the normalized SUV (nSUV) was calculated as the ratio of SUVmax inside the GTV to the SUVmean of adjacent three-dimensional shells of thickness 5 mm/10 mm/20 mm as a measure of signal to background contrast. Targets were suitable for BgRT if (1) nSUV was larger than an nSUV threshold and (2) non-tumour tissue inside adjacent shell was free of PET-avid uptake.ResultsOf this cohort of 84 patients, 24 had at least one pelvic node or metastatic site disease, 1 to 13 lesions per patient, with a total of 98 lesions (60 pelvic nodes/38 extra-pelvic nodal diseases and haematogenous metastases). Target volumes ranged from 0.08 to 9.6 cm3 while SUVmax ranged from 2.1 to 55.0. nSUV ranged from 1.9 to 15.7/2.4 to 25.7/2.5 to 34.5 for the 5 mm/10 mm/20 mm shell expansion. Furthermore, 74%/68%/34% of the lesions had nSUV ≥ 3 and were free of PSMA PET uptake inside the GTV outer shell margin expansion of 5 mm/10 mm/20 mm. Adjacent avid organs were another lesion, bladder, bowel, ureter, prostate, and liver.ConclusionsThe majority of PSMA PET/CT-defined radiotherapy targets would be suitable for BgRT by using a 10-mm tracking zone in prostate cancer. A subset of lesions had adjacent non-tumour uptake, mainly due to the proximity of ureter or bladder, and may require exclusion from emission tracking during BgRT.

Apalutamide, Darolutamide and Enzalutamide for Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC): A Critical Review.

Simple SummaryApalutamide, darolutamide and enzalutamide are androgen-receptor signaling inhibitors proved to be useful in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). Although computed tomography and bone scans have been used to identify patients with nmCRPC in pivotal trials, currently, novel imaging techniques are widely used to stage patients, and they can detect metastases in many men with nmCRPC who are negative to conventional imaging. This review aims at discussing the role of apalutamide, darolutamide and enzalutamide in nmCRPC and the clinical implications of novel imaging techniques during treatment choice. Nonmetastatic castration-resistant prostate cancer (nmCRPC) represents a condition in which patients with prostate cancer show biochemical progression during treatment with androgen-deprivation therapy (ADT) without signs of radiographic progression according to conventional imaging. The SPARTAN, ARAMIS and PROSPER trials showed that apalutamide, darolutamide and enzalutamide, respectively, prolong metastasis-free survival (MFS) and overall survival (OS) of nmCRPC patients with a short PSA doubling time, and these antiandrogens have been recently introduced in clinical practice as a new standard of care. No direct comparison of these three agents has been conducted to support treatment choice. In addition, a significant proportion of nmCRPC on conventional imaging is classified as metastatic with new imaging modalities such as the prostate-specific membrane antigen positron emission tomography (PSMA-PET). Some experts posit that these “new metastatic” patients should be treated as mCRPC, resizing the impact of nmCRPC trials, whereas other authors suggest that they should be treated as nmCRPC patients, based on the design of pivotal trials. This review discusses the most convincing evidence regarding the use of novel antiandrogens in patients with nmCRPC and the implications of novel imaging techniques for treatment selection.

Robot-assisted Prostate-specific Membrane Antigen–radioguided Salvage Surgery in Recurrent Prostate Cancer Using a DROP-IN Gamma Probe: The First Prospective Feasibility Study

BackgroundIt has been proven that intraoperative prostate-specific membrane antigen (PSMA)-targeted radioguidance is valuable for the detection of prostate cancer (PCa) lesions during open surgery. Rapid extension of robot-assisted, minimally invasive surgery has increased the need to make PSMA-radioguided surgery (RGS) robot-compliant. ObjectiveTo evaluate whether the miniaturized DROP-IN gamma probe facilitates translation of PSMA-RGS to robotic surgery in men with recurrent PCa. Design, setting, and participantsThis prospective feasibility study included 20 patients with up to three pelvic PCa recurrences (nodal or local) on staging PSMA positron emission tomography (PET) after previous curative-intent therapy. Surgical procedureRobot-assisted PSMA-RGS using the DROP-IN gamma probe was carried out 19–23 h after intravenous injection of 99mtechnetium PSMA-Investigation & Surgery (99mTc-PSMA-I&S). MeasurementsThe primary endpoint was the feasibility of robot-assisted PSMA-RGS. Secondary endpoints were a comparison of the radioactive status (positive or negative) of resected specimens and final histopathology results, prostate-specific antigen (PSA) response following PSMA-RGS, and complications according to the Clavien-Dindo classification. Results and limitationsUsing the DROP-IN probe, 19/21 (90%) PSMA-avid lesions could be resected robotically. On a per-lesion basis, the sensitivity and specificity of robot-assisted PSMA-RGS was 86% and 100%, respectively. A prostate-specific antigen (PSA) reduction of >50% and a complete biochemical response (PSA <0.2 ng/ml) were seen in 12/18 (67%) and 4/18 (22%) patients, respectively. During follow-up of up to 15 mo, 4/18 patients (22%) remained free of biochemical recurrence (PSA ≤0.2 ng/ml). One patient suffered from a Clavien-Dindo grade >III complication. ConclusionsThe DROP-IN probe helps in realizing robot-assisted PSMA-RGS. The procedure is technically feasible for intraoperative detection of nodal or local PSMA-avid PCa recurrences. Patient summaryA device called the DROP-IN probe facilitates minimally invasive, robot-assisted surgery guided by radioactive tracers in patients with recurrent prostate cancer. This procedure holds promise for improving the intraoperative identification and removal of prostate cancer lesions.

Cohort study of oligorecurrent prostate cancer patients: Oncological outcomes of patients treated with salvage lymph node dissection via PSMA radioguided surgery.

106 Background: Prostate-specific membrane antigen (PSMA) positron-emission tomography (PET) allows detection of small and/or atypically localized metastatic prostate cancer (PCa) lesions. In a subset of patients with recurrent oligometastatic PCa salvage surgery with PSMA-targeted radioguidance (PSMA-RGS) may be of value. We aimed to evaluate the oncological outcomes of salvage PSMA-RGS for oligorecurrent PCa and determine predictive preoperative factors of improved outcomes. Methods: In this cohort study within two tertiary care centers, patients with biochemical recurrence (BCR) after radical prostatectomy (RP) and imaging with PSMA PET receiving salvage PSMA-RGS between 2014 and 2020 were analyzed. Kaplan-Meier and multivariable Cox regression models adjusted for various parameters were used to test for BCR-free survival (BFS) and therapy-free survival (TFS) differences. Postoperative complications were classified according to Clavien-Dindo. Results: Overall, 364 patients were assessed. At PSMA-RGS, median (IQR) age and preoperative PSA was 67 (61-71) years and 1.0 (0.5-1.9) ng/ml. Metastatic soft-tissue lesions were removed in 356 (94.4%) patients. Within three months from surgery, 25 (6.6%) patients suffered from Clavien-Dindo complications grade III-IV. During follow-up, 235 patients experienced BCR and 129 patients received further therapy. Median follow-up for patients who did not experience BCR and who did not receive further therapy was 11.1 months and 10.5 months, respectively. Median (IQR) BFS and TFS was 7.8 (5.4-10.9) and 34.9 (24.7-43.5) months. At two years of follow-up, BFS rate was 31.9% and TFS rate was 56.6%. In multivariable analyses, higher preoperative PSA (HR: 1.06), higher number of PSMA-avid lesions on preoperative imaging (HR: 1.2) and multiple (pelvic plus retroperitoneal) localizations (HR: 1.7), as well as retroperitoneal localization (HR: 2.0) of lesions in PSMA PET imaging were independent predictors of BCR after PSMA-RGS. Limitations are the retrospective design and lack of a control group. Conclusions: As salvage surgery in oligorecurrent PCa currently constitutes an experimental treatment approach careful patient selection is mandatory based on life expectancy, low PSA values and low number of PSMA PET avid lesions located in the pelvis. Further studies are needed to confirm our findings and define the oncological value of salvage surgical procedures in oligorecurrent PCa.

Considerations on Integrating Prostate-Specific Membrane Antigen Positron Emission Tomography Imaging Into Clinical Prostate Cancer Trials by National Clinical Trials Network Cooperative Groups.

As prostate-specific membrane antigen (PSMA) positron emission tomography (PET) becomes increasingly available in the United States, the greater sensitivity of the technology in comparison to conventional imaging poses challenges for clinical trials. The NCI Clinical Imaging Steering Committee (CISC) PSMA PET Working Group was convened to coordinate the identification of these challenges in various clinical scenarios and to develop consensus recommendations on how best to integrate PSMA PET into ongoing and upcoming National Clinical Trials Network (NCTN) trials. NCI CISC and NCI Genitourinary Steering Committee members and leadership nominated clinicians, biostatisticians, patient advocates, and other imaging experts for inclusion in the PSMA PET Working Group. From April to July 2021, the working group met independently and in conjunction with the CISC to frame challenges, including stage migration, response assessment, trial logistics, and statistical challenges, and to discuss proposed solutions. An anonymous, open-ended survey was distributed to members to collect feedback on challenges faced. Representatives from each NCTN group were invited to present an overview of affected trials. From these discussions, the consensus document was developed and circulated for the inclusion of multiple rounds of feedback from both the Working Group and CISC. The current consensus document outlines the key challenges for clinical prostate cancer trials resulting from the increasing availability of PSMA PET. We discuss implications for patient selection and definition of end points and provide guidance and potential solutions for different clinical scenarios, particularly with regard to best practices in defining eligibility criteria and outcome measures. This article provides guidance regarding clinical trial design and conduct, and the interpretation of trial results.

Patterns of Prostate Cancer Recurrence After Brachytherapy Determined by Prostate-Specific Membrane Antigen–Positron Emission Tomography and Computed Tomography Imaging

The aim of this study was to characterize the patterns of prostate cancer recurrence after brachytherapy (BT) using 2-(3-[1-carboxy-5-([6-18F-fluoropyridine-3-carbonyl]-amino)-pentyl]-ureido)-pentanedioic acid ([18F]DCFPyL) prostate-specific membrane antigen (PSMA) positron emission tomography (PET) and computed tomography (CT) imaging. Patients were selected from an ongoing prospective institutional trial investigating the use of [18F]DCFPyL PSMA PET and CT in recurrent prostate cancer (NCT02899312). This report included patients who underwent BT (either monotherapy or boost) and experienced a biochemical failure (BF) defined by the Phoenix definition (prostate-specific antigen [PSA] > 2 ng/mL above nadir). Between March 2017 and April 2020, 670 patients underwent [18F]DCFPyL PSMA PET and CT imaging. Of these 670 patients, 93 were treated with BT; 73 underwent monotherapy, and 20 underwent BT boost (19 low-dose rate and 1 high-dose rate). To report on patterns of recurrence outcomes, 86 patients (median prescan PSA 6.0) with a positive [18F]DCFPyL PSMA PET and CT scan and true BF were included. The most common location of relapse was local; 62.8% had a component of local failure (defined as prostate and/or seminal vesicles), and 46.5% had isolated local failure only, with no other sites of involvement. Regional failure occurred in 40.7% of patients, and 36.0% had metastatic failure. Isolated local recurrence was seen in 54.3% of monotherapy patients versus only in 12.5% of boost patients. Metastatic failure was seen in 28.6% of monotherapy patients versus 68.8% of the boost patients. Local recurrences (69.0%) were found within the same prostate biopsy sextant involved with the tumor at diagnosis, and 76.0% of patients with seminal vesicle recurrences had prostate-base involvement at diagnosis. Contrary to previous evidence, our study suggests that in prostate BT patients with biochemical recurrence, the most common site of failure is local for the patients treated with monotherapy and metastatic for patients treated with a combination of external beam radiation and BT boost.

Prostate-specific Membrane Antigen Positron Emission Tomography (PSMA-PET) and Gleason grading system based Artificial Intelligence (AI) model in diagnosis and staging of prostate cancer

Introduction: Prostate cancer is the second-most commonly occurring cancer and the fifth major cause of death among men worldwide. Early diagnosis and treatment planning are very crucial in reducing the mortality rate due to prostate cancer. Gleason grading is the most used prostate cancer prognosis tool by doctors for a long time. It is used to determine the aggressiveness of the cancer for planning treatment options. The process requires very trained pathologists to look at multiple biopsy samples under the microscope and assign a grade to the cancer based on its severity.Methods: In this work, we are adding Gleason grading capabilities to prostate-specific membrane antigen positron emission tomography/ computed tomography (PSMA PET-CT) scans for tumor habitats and classify them as aggressive or indolent type. Tagging habitats with Gleason grade to categorize them as aggressive or indolent type helps in biopsy planning to extract the right tissue samples and tagging helps to target aggressive tumors during radiation therapy. We have developed a machine learning-based model to automatically classify tumor habitat regions of interest from PSMA PET and CT imaging data into Gleason grade groups of indolent and aggressive.Results: The 68Ga-PSMA PET-CT scans are very effective in detecting the presence of different habitats within the tumor with distinct volumes, each with a specific combination of flow, cell density, necrosis, and edema. Habitat distribution through tumor heterogeneity analysis in patients with prostate cancers can be enabled to discriminate between cancers that progress quickly and those that are more indolent.Conclusion: We have developed an AI model to classify habitat tumors present in the gross tumor volume into indolent and aggressive types based on the ground truth generated using Gleason grade groups on pathology samples by Healthcare Global Cancer Hospital, Bangalore, India. Habitat analysis helps radiotherapists to target active tumor cells within gross tumor volume and helps in selecting the right tissue for performing biopsy. The currently developed model is performing with an overall accuracy of 90% on test data.

Frequency and intensity of [18F]-PSMA-1007 uptake after COVID-19 vaccination in clinical PET.

Objectives:To assess the frequency and intensity of [18F]-prostate-specific membrane antigen (PSMA)-1007 axillary uptake in lymph nodes ipsilateral to COVID-19 vaccination with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) in patients with prostate cancer referred for oncological [18F]-PSMA positron emission tomography (PET)/CT or PET/MR imaging.Methods:126 patients undergoing [18F]-PSMA PET/CT or PET/MR imaging were retrospectively included. [18F]-PSMA activity (maximum standardized uptake value) of ipsilateral axillary lymph nodes was measured and compared with the non-vaccinated contralateral side and with a non-vaccinated negative control group. [18F]-PSMA active lymph node metastases were measured to serve as quantitative reference.Results:There was a significant difference in maximum standardized uptake value in ipsilateral and compared to contralateral axillary lymph nodes in the vaccination group (n = 63, p < 0.001) and no such difference in the non-vaccinated control group (n = 63, p = 0.379). Vaccinated patients showed mildly increased axillary lymph node [18F]-PSMA uptake as compared to non-vaccinated patients (p = 0.03). [18F]-PSMA activity of of lymph node metastases was significantly higher (p < 0.001) compared to axillary lymph nodes of vaccinated patients.Conclusion:Our data suggest mildly increased [18F]-PSMA uptake after COVID-19 vaccination in ipsilateral axillary lymph nodes. However, given the significantly higher [18F]-PSMA uptake of prostatic lymph node metastases compared to “reactive” nodes after COVID-19 vaccination, no therapeutic and diagnostic dilemma is to be expected.Advances in knowledge:No specific preparations or precautions (e.g. adaption of vaccination scheduling) need to be undertaken in patients undergoing [18F]-PSMA PET imaging after COVID-19 vaccination.

Radiolabeling of PSMA-617 with 89Zr: A novel use of DMSO to improve radiochemical yield and preliminary small-animal PET results

IntroductionNovel diagnostic and therapeutic options are urgently needed for patients with metastatic castration-resistant prostate cancer (CRPC). PSMA-617 is one of the most promising ligands that bind to prostate specific membrane antigen (PSMA), the cell surface biomarker of CRPC. Of the radiolabeled PSMA ligands developed to date, [68Ga]Ga-PSMA-617 is most commonly used for PSMA positron emission tomography (PET) prior to radioligand therapy (RLT) with [177Lu]Lu-PSMA-617. However, the presence of 68Ga radioactivity (half-life 68 m) in urine at the early PET imaging time point complicates optimization of the therapeutic dose of PSMA-617 labeled with 177Lu (half-life 6.7 d). Thus, PET imaging with the long-lived positron emitter 89Zr (half-life 3.3 d) would be better suited in order to optimize the dose of [177Lu]Lu-PSMA-617 as 89Zr PET allows scans after excretion of the radioactive urine. Until now, PSMA-617 could not be radiolabeled with 89Zr with high radiochemical yield due to poor incorporation of 89Zr into 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Here we report a novel method for radiolabeling PSMA-617 with 89Zr and the preliminary results of small-animal PET with [89Zr]Zr-PSMA-617. MethodsWe labeled PSMA-617 with 89Zr in a 1:1 mixture of DMSO and HEPES buffer at 90 °C for 30 min, followed by quality control analysis by HPLC. We then determined the dissociation constant (Kd) and logD values of [89Zr]Zr-PSMA-617. We obtained PET images of [89Zr]Zr-PSMA-617 at 24 h in mice bearing both LNCaP (PSMA-positive) and PC-3 (PSMA-negative) tumors (N = 5). The ex vivo [89Zr]Zr-PSMA-617 biodistribution was then examined separately using tissue samples of LNCaP-bearing mice at 2 h (N = 4) and 24 h (N = 4). Results[89Zr]Zr-PSMA-617 was prepared with a radiochemical yield of 70 ± 9%. The Kd value was 6.8 ± 3.5 nM. The logD value was −4.05 ± 0.20. PET images showed the highest uptake in LNCaP tumors (maximum standardized uptake value, SUVmax = 0.98 ± 0.32) and low uptake in kidneys (SUVmax = 0.18 ± 0.7) due to the absence of urine radioactivity. Conclusion[89Zr]Zr-PSMA-617 was successfully prepared using DMSO and HEPES buffer. [89Zr]Zr-PSMA-617 visualized PSMA-positive LNCaP tumors in the absence of radioactive urine 24 h p.i. Advances in knowledge and implications for patient careThis method of radiolabeling PSMA-617 with 89Zr using DMSO would be suitable for future clinical trials. Prediction of radiation dose by using [89Zr]Zr-PSMA-617 leads to the safe and effective RLT with [177Lu]Lu-PSMA-617.

Stereotactic Radiotherapy to Oligoprogressive Lesions Detected With 68Ga-PSMA-PET/CT in Castration-Resistant Prostate Cancer Patients

Few studies have investigated the feasibility of MDT in metastatic castration-resistant prostate cancer (CRPC) patients with heterogeneous patient populations with different treatment strategies and various imaging modalities other than gallium prostate-specific membrane antigen-positron emission tomography (68Ga-PSMA-PET/CT) for detecting oligoprogressive lesions. We assessed the outcomes of stereotactic body radiotherapy (SBRT) to treat oligoprogressive castration-resistant prostate cancer (CRPC) patients with ≤5 lesions using 68Ga-PSMA-PET/CT.The clinical data of 67 CRPC patients with 133 lesions treated with 68Ga-PSMA-PET/CT-based SBRT were retrospectively analyzed. All of the patients had oligoprogressive disease during androgen-deprivation therapy (ADT). The inclusion criteria were as follows: a histologic diagnosis of PC on primary tumor biopsy, less than or equal to 5 bone and/or lymph node metastases detected with 68Ga-PSMA-PET/CT during ADT, being castration-resistant according to the European Association of Urology guidelines, a controlled primary tumor, SBRT fraction doses of at least 6 Gy per fraction and a biologically effective dose (BED) of at least 90 Gy using α⁄β of 3 Gy. The prognostic factors for overall- (OS) and progression-free survival (PFS) and the predictive factors for switching to next-line systemic treatment (NEST) and NEST-free survival (NEST-FS) were analyzed.With a median follow-up of 17.5 months, the 2-year overall survival (OS) and PFS rates were 86.9% and 34.4%, respectively. Most of the patients had GS 9 or 10 tumors and locally advanced disease. The most frequent oligoprogressive site was bone only (64.2%), and more than half of the patients (53.7%) had a single metastasis. The median number of metastases was 1 (range, 1-5). In the case of bone metastasis, the most adopted methods were single-dose 16 Gy and 18 Gy, and the most adopted prescription for nodal metastasis was 30-35 Gy delivered in 5 fractions. The PSA response after SBRT was observed in 49 patients (73.1%). Progression was observed in 37 patients (55.2%) at a median of 11.0 months following SBRT. Forty-five patients (67.2%) remained on ADT after SBRT, and 22 patients (32.8%) had a NEST change at a median of 16.4 months after MDT. Patients with a NEST change had higher post-SBRT PSA values and fewer PSA nadirs after MDT than their counterparts. In multivariate analysis, higher pre-SBRT PSA values were the only significant predictor for worse OS and NEST-FS, and no significant factor was found for PFS. No serious acute or late toxicities were observed.This study demonstrated the feasibility of MDT using SBRT to treat oligoprogressive lesions by 68Ga-PSMA-PET/CT in CRPC patients is efficient and well-tolerated, prolonging the effectiveness of ADT by delaying NEST.

Early Outcomes and Decision Regret Using PSMA/MRI-Guided Focal Boost for Prostate Cancer SBRT

PurposeStereotactic body radiation therapy (SBRT) is a recognized treatment for low- and intermediate-risk prostate cancer, with 36.25 Gy in 5 fractions the most commonly used regimen. We explored the preliminary efficacy, patient recorded toxicity, and decision regret in intermediate- and high-risk prostate cancer receiving SBRT with prostate-specific membrane antigen (PSMA)/magnetic resonance imaging (MRI) guided focal gross tumor volume boost to 45 Gy. Methods and MaterialsBetween July 2015 and June 2019, 120 patients received SBRT across 2 institutions with a uniform protocol. All patients had fiducial markers and hydrogel, MRI and PSMA positron emission tomography (PET) scan. All patients received a questionnaire asking the degree of urinary, bowel, and sexual bother experienced at set time points, including questions about treatment choice and decision regret. ResultsOne hundred twelve of 120 patients consented. Their median age was 72 years and median follow-up was 2.3 years. As per National Comprehensive Cancer Network guidelines, 78% had intermediate risk and 20% high risk. Androgen deprivation was combined with radiation in 6 patients. Most patients (74%) reported that receiving SBRT significantly influenced their choice of treatment. Five men (4%) expressed “quite a lot” (n = 4) or “very much” regret (n = 1) regarding their choice of treatment, while 89% expressed “no regret.” Similar to pretreatment levels, “quite a lot” or “very much” urinary or bowel bother was expressed in 8% and 6% of patients, respectively. Two patients experienced nadir +2 biochemical failure, both found to have bone metastases. A third patient underwent PSMA PET at nadir +1.7 and had disease at the penile bulb, which was out of field. Three year estimated freedom from biochemical failure was 99% for intermediate and 85% for high-risk groups. ConclusionsWe have demonstrated promising efficacy and low toxicity with PSMA/MRI-guided SBRT focal boost. Less than 5% of patients expressed significant decision regret for their choice of treatment.

PD57-01 PREDICTING EARLY BIOCHEMICAL PROGRESSION IN PROSTATE CANCER PATIENTS STAGED WITH PSMA PET AND MULTIPARAMETRIC MAGNETIC RESONANCE IMAGING

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy IV (PD57)1 Sep 2021PD57-01 PREDICTING EARLY BIOCHEMICAL PROGRESSION IN PROSTATE CANCER PATIENTS STAGED WITH PSMA PET AND MULTIPARAMETRIC MAGNETIC RESONANCE IMAGING Dennie Meijer, Pim van Leeuwen, Maarten Donswijk, Thierry Boellaard, Ivo Schoots, Henk van der Poel, Harry Hendrikse, Daniela Oprea-Lager, and André Vis Dennie MeijerDennie Meijer More articles by this author , Pim van LeeuwenPim van Leeuwen More articles by this author , Maarten DonswijkMaarten Donswijk More articles by this author , Thierry BoellaardThierry Boellaard More articles by this author , Ivo SchootsIvo Schoots More articles by this author , Henk van der PoelHenk van der Poel More articles by this author , Harry HendrikseHarry Hendrikse More articles by this author , Daniela Oprea-LagerDaniela Oprea-Lager More articles by this author , and André VisAndré Vis More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002091.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The aim of this study was to point out predictors for early oncological outcome in patients who opt for robot-assisted laparoscopic radical prostatectomy (RARP) for localized prostate cancer (PCa) including conventional prognostic variables as well as multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging. METHODS: This observational study included 500 patients who underwent RARP and extended pelvic lymph node dissection (ePLND). Outcome measurement was biochemical progression of disease, defined as any post-operative PSA ≥0.2 ng/mL. A Cox-regression analysis was performed to assess predictors for biochemical progression, including initial prostate-specific antigen (PSA)-value, biopsy Grade Group (GG), T-stage on mpMRI, and lymph node status on PSMA PET imaging (miN0 vs. miN1). RESULTS: The median total follow-up of all included patients was 12.8 months (IQR 6.6-22.3). When assessing biochemical progression after surgery, initial PSA-value (per doubling; OR 1.24 (95%CI 1.08-1.43), p=0.003), biopsy GG ≥4 vs. GG 1-2 (OR 2.33 (95%CI 1.47-3.69), p<0.001), T-stage on mpMRI (rT3a vs. rT2: OR 2.04 (95%CI 1.30-3.20), p=0.002; ≥rT3b vs. rT2: OR 4.87 (95%CI 3.24-7.32), p<0.001) and miN1 on PSMA PET imaging (OR 2.16 (95%CI 1.46-3.20), p<0.001) were independent predictors of biochemical progression of disease. Moreover, the number of pelvic lymph node metastases on PSMA PET was significantly associated with biochemical progression: one pelvic lymph node metastasis vs. no metastatic disease resulted in an OR 2.60 (95%CI 1.57-4.31), p<0.001; two pelvic lymph node metastases or more on PSMA PET vs. no metastatic disease resulted in an OR 4.61 (95%CI 2.84-7.48), p<0.001. CONCLUSIONS: Initial PSA-value, biopsy GG ≥4, ≥rT3 disease on mpMRI and miN1 disease on PSMA PET were predictors for early biochemical progression after RARP. Furthermore, the number of pelvic lymph node metastases on staging PSMA PET was associated with biochemical progression. Identifying patients with an increased risk of biochemical progression after surgery may have implications for patient counseling in radical treatment decisions and on patient selection for modern (neo-)adjuvant and systematic treatments. Source of Funding: No funding was received for conducting this study. © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1009-e1009 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Dennie Meijer More articles by this author Pim van Leeuwen More articles by this author Maarten Donswijk More articles by this author Thierry Boellaard More articles by this author Ivo Schoots More articles by this author Henk van der Poel More articles by this author Harry Hendrikse More articles by this author Daniela Oprea-Lager More articles by this author André Vis More articles by this author Expand All Advertisement Loading ...

MP11-14 VERY LOW PROSTATE PET CT PSMA EXPRESSION MAY BE MISLEADING IN STAGING PROSTATECTOMY CANDIDATES

You have accessJournal of UrologyProstate Cancer: Staging (MP11)1 Sep 2021MP11-14 VERY LOW PROSTATE PET CT PSMA EXPRESSION MAY BE MISLEADING IN STAGING PROSTATECTOMY CANDIDATES Rennen Haramaty, Alon Lazarovich, Asaf Shvero, Miki Haifler, Jonathan Gal, Shay Golan, Sagi Shpitzer, Azik Hoffman, Omri Nativ, Yuval Freifeld, Rani Zreik, Zohar Dotan, and Barak Rosenzweig Rennen HaramatyRennen Haramaty More articles by this author , Alon LazarovichAlon Lazarovich More articles by this author , Asaf ShveroAsaf Shvero More articles by this author , Miki HaiflerMiki Haifler More articles by this author , Jonathan GalJonathan Gal More articles by this author , Shay GolanShay Golan More articles by this author , Sagi ShpitzerSagi Shpitzer More articles by this author , Azik HoffmanAzik Hoffman More articles by this author , Omri NativOmri Nativ More articles by this author , Yuval FreifeldYuval Freifeld More articles by this author , Rani ZreikRani Zreik More articles by this author , Zohar DotanZohar Dotan More articles by this author , and Barak RosenzweigBarak Rosenzweig More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001984.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: 68Ga-labeled prostate-specific membrane antigen (PSMA) positron-emission tomography (PET) computed tomography (CT) imaging quickly earns an important role in staging radical prostatectomy candidates. While PSMA is generally weakly expressed in normal prostate tissue, it is strongly upregulated in prostate cancer. However, some clinically significant prostate cancers exemplify low reads on PSMA PET CT. In the current work we evaluate this unique sub-population of patients with ‘negative’ prostate PSMA PET CT reads. METHODS: We retrospectively reviewed 392 patients who underwent radical prostatectomy between September 2014 to July 2019 in 5 medical centres.Patients with pre-operative PSMA PET CT imaging were included. We collected data on baseline characteristics including demographics, comorbidities, prostate specific antigen (PSA) and rectal exam, prior biopsies, imaging results, and biopsies and radical prostatectomy histology. An index group of patients with ‘negative’ PSMA PET CT prostate read was defined as “scarce” uptake and/or numerically maximal standardized uptake value (SUVmax) below physiologic uptake. For control we used patients with PSMA PET CT prostate read defined as “intense” and/or numerically as SUVmax above physiologic uptake. RESULTS: 97 patients had PSMA PET CT imaging prior surgery, 52 (54%) of whom fitted with the index group inclusion criteria and 45 (46%) with the control group. All pre-operative characteristics did not significantly differ in-between groups except lesion size and SUVmax per PSMA PET CT (Table1). Prostatectomy specimen’s histology analysis significantly differed in-between groups, for ISUP score, seminal vesicles invasion, T stage and positive margins rates (p<0.05).Nonetheless, 50 (96%) of the index group patients harbored clinically significant disease (ISUP>=2) with extra-prostatic disease showed in 24 (46%) and peri-neural invasion in 35 (67%).Positive lymph nodes were found in 4 (8%) of index group patients. CONCLUSIONS: While prostate cancer aggressiveness was generally correlated with intense uptake of PSMA on pre-operative PSMA/PET CT, a subpopulation of patients with clinically significant cancer and aggressive characteristics show weak reads only on this imaging. These data raise concern applying PSMA PET CT for staging of prostatectomy candidates. Source of Funding:- © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e184-e184 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rennen Haramaty More articles by this author Alon Lazarovich More articles by this author Asaf Shvero More articles by this author Miki Haifler More articles by this author Jonathan Gal More articles by this author Shay Golan More articles by this author Sagi Shpitzer More articles by this author Azik Hoffman More articles by this author Omri Nativ More articles by this author Yuval Freifeld More articles by this author Rani Zreik More articles by this author Zohar Dotan More articles by this author Barak Rosenzweig More articles by this author Expand All Advertisement Loading ...

Positron emission tomography with computed tomography/magnetic resonance imaging for primary staging of prostate cancer

Prostate cancer is the most common malignancy and the second leading cause of cancer-related death in men. Accurate imaging diagnosis and staging are crucial for patient management and treatment. The role of nuclear medicine in the diagnosis of prostate cancer has evolved rapidly in recent years due to the availability of hybrid imaging with radiopharmaceuticals targeting the prostate-specific membrane antigen (PSMA). Hybrid imaging provides higher diagnostic accuracy compared to conventional imaging and has a significant impact on clinical management. Numerous radiotracers have been used in clinical applications, with PSMA ligands being the most commonly used. Hybrid imaging provides higher diagnostic accuracy for lymph node and bone metastases compared to conventional imaging and has asignificant impact on clinical management. The high accuracy for primary staging in high-risk prostate cancer using PSMA ligands has led to the inclusion of PSMA positron emission tomography (PET)/computed tomography (CT) in the new German S3 guideline for primary staging of prostate cancer. The aim of this article is to provide an overview of the use of PET imaging in the primary diagnosis of prostate cancer, to present the most commonly used radiotracers, and to highlight the results of recent studies.