Use Of Prostate-specific Membrane Antigen Research Articles

Abstract A010: Prostate-specific membrane antigen use in glioma management: past, present, and future

Abstract Introduction: Prostate-Specific Membrane Antigen (PSMA) is a type II membrane-bound zinc metallopeptidase expressed in various tissues, including the prostate, renal tubular epithelium, small and large intestinal mucosa, and brain. It plays a role in cell proliferation pathways and folate and glutamate metabolism. PSMA has been utilized for imaging and treatment of prostate cancer and is also expressed in solid tumor neovasculature of other cancers. Gliomas, which are central nervous system neoplasms of glial tissue, represent a challenging group of tumors with limited treatment options due to their invasive nature. PSMA's ability to internalize and location makes it a promising diagnostic and therapeutic target for gliomas. This review synthesizes the literature surrounding the use of PSMA in gliomas to inform current and future directions of study. Methods: A review of the literature was conducted using PubMed and Scopus databases in June 2023. Seventy-one relevant studies, including histopathological, imaging, and therapeutic investigations, were identified. These publications were categorized by year of publication to analyze the evolution of PSMA research in glioma management. Additionally, clinicaltrials.gov was searched for ongoing clinical trials involving PSMA and gliomas. Results: Histopathological studies have demonstrated PSMA's high expression in glioma vasculature, particularly in glioblastoma (GBM), a high-grade glioma (HGG). Studies have investigated PSMA's role in tumor metabolism and its interplay with other tumor markers. Some research suggests that high PSMA expression in GBM endothelium may promote angiogenesis and correlates with poor prognosis. PSMA PET imaging has shown promise in diagnosing and differentiating HGGs and low-grade gliomas (LGGs). Studies have reported high sensitivity and diagnostic accuracy of PSMA PET for HGGs, making it a potentially useful screening tool for radioligand therapy patient selection. Mouse models have also been employed to evaluate the utility of PSMA PET imaging in GBM, with some studies suggesting its application in defining non-enhancing portions of tumors and recurrence volume. PSMA-targeted therapies, particularly PSMA-targeted radiotherapy using radionuclide agents like 177Lu-PSMA-617, have been explored for the treatment of gliomas. Case reports and preliminary studies have demonstrated potential efficacy and tumor response to such therapies, warranting further investigation. Conclusion: The evolving literature indicates that PSMA holds promise as a valuable tool in the diagnosis, prognosis, and treatment of gliomas. Studies have highlighted PSMA PET imaging's high diagnostic accuracy and its potential in patient selection for targeted therapies. However, more research is needed to fully understand the role of PSMA in glioma behavior and to optimize treatment strategies. Ongoing clinical trials and future investigations will further our knowledge of PSMA's potential in managing gliomas and improving patient outcomes. Citation Format: Joshua D. McBriar, Neeva Shafiian, Steven Scharf, A. Gabriella Wernicke. Prostate-specific membrane antigen use in glioma management: past, present, and future [abstract]. In: Proceedings of the AACR Special Conference on Brain Cancer; 2023 Oct 19-22; Minneapolis, Minnesota. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_1):Abstract nr A010.

Location of Local Recurrences Post-Prostatectomy Detected by 18F-DCPFyL and Implications for Salvage Radiotherapy Target Volumes.

The use of prostate-specific membrane antigen (PSMA) PET scans have improved detection of recurrent prostate cancer for biochemical failure post-prostatectomy. The primary aim of this study is to assess the location of local recurrences for PSMA PET positive disease post-prostatectomy relative to anatomical landmarks and to inform salvage radiotherapy contouring guidelines. This is a retrospective study of patients who underwent a staging PSMA PET-CT scan with 18F-DCFPyL tracer. Eligible patients included men with biochemical recurrence (PSA >0.2ng/mL) post-prostatectomy for prostate adenocarcinoma. PSMA positive local disease (GTV) was marked on the CT scan of the PSMA PET/CT, using the PSMA PET scan fused as the secondary dataset. Reference structures were contoured to compare the positional relationship to the GTV local recurrence. Centroids of each GTV position were measured to the closest border of the reference structures and distance measured. Forty-five patients had a local recurrence on PSMA PET, 28/45 with prostate bed recurrence and 17/45 with seminal vesicle bed recurrence. The median age was 72.7 years, median pre-treatment PSA 0.515 ng/ml (0.2-11.1), pT2 in 37.8% and pT3 in 62.2, ISUP G2-3 was 66.7%, ISUP 4-5 29.6%, 67% ECE, 15.4% SV involvement and 40% positive margin. For prostate bed recurrences, 93.6% of GTVs were within 15mm from the inferior border of pubic symphysis (median 3.3mm [-9.8-15.4]), 83.9% within 10mm from the VUA (median 3.3mm [-17.4-15.9]), and 80.6% were greater than 10mm from the most superior slice of the penile bulb (median 16.4mm [1-29.5]). Laterally, 83.9% of recurrences were within 10mm of midline and 41.9% within 5mm (median 3.3mm [-13.56-11.59]) and all were contained within levator, 35.5% within 5mm (median 7.7 [1-22.6]) of the medial muscle border. 29.0% were within 5mm from the anterior edge of the rectal wall (median -7mm [-32.3-0.5]). Seminal vesicle bed recurrences were within 17.5mm of upper border of pubic symphysis for 88.9% of patients (median -4.69mm[-30.8to18.2]), 100% were more than 7.5mm inferiorly from the vas deferens (median-22.1mm[-32.7to-7.7]). Laterally, 100% recurrences were more than 7.5mm medial from obturator internus (median 5.37mm [-23.1to37.8]), and 88.9% were more than 10mm from midline (median 23.1mm [2.0-36.6]). The 18F-DCFPyL PSMA PET local recurrences can provide detailed localization of prostate bed and seminal vesicle recurrences. Our data can inform contouring guidelines for salvage radiotherapy to the prostate bed, particularly when using anatomical landmarks to define cranio-caudal extent of target volumes. For target volume laterally, the medial wall of levator ani would encompass all prostate bed recurrences, and no seminal vesicles recurrences were seen at the medial border of the obturator internus muscle.

Clinical impact of Prostate-Specific Membrane Antigen Positron Emission Tomography (PET) on intensification or deintensification of advanced renal cell carcinoma management

PurposeThere is an emerging role of the use of Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) in renal cell carcinoma. Herein, we report our experience in use of PSMA PET in recurrent or metastatic renal cell carcinoma (RCC).MethodsA retrospective analysis of all patients who underwent PSMA PET for suspected recurrent or de-novo metastatic RCC between 2015 and 2020 at three institutions was performed. The primary outcome was change in management (intensification or de-intensification) following PSMA PET scan. Secondary outcomes included histopathological correlation of PSMA avid sites, comparison of sites of disease on PSMA PET to diagnostic CT and time to systemic treatment.Results

The Impact of PSMA PET/CT on Modern Prostate Cancer Management and Decision Making—The Urological Perspective

Prostate-specific membrane antigen (PSMA) PET use in prostate cancer treatment has recently become a routinely used imaging modality by urologists. New, established data regarding its performance in different stages of prostate cancer, as well as gaining clinical knowledge with new tracers, drives the need for urologists and other clinicians to improve the utilization of this tool. While the use of PSMA PET/CT is more common in metastatic disease, in which it outperforms classical imaging modalities and drives treatment decisions and adjustments, recently, it gained ground in localized prostate cancer as well, especially in high-risk disease. Still, PSMA PET/CT might reveal lesions within the prostate or possibly locoregional or metastatic disease, not always representing true cancer when utilized in earlier stages of the disease, potentially adding diagnostic burden and changing treatment decisions. As urological treatment options advance toward focal treatments in localized organ-confined prostate cancer, recent reports suggest the utilization of PSMA PET/CT in treatment planning and follow-up and even when choosing active surveillance. This review aims to reveal the current perspective of urologists regarding its daily use.

177Lu]Lu-PSMA Therapy as an Individual Treatment Approach for Patients with High-Grade Glioma: Dosimetry Results and Critical Statement.

The theranostic use of prostate-specific membrane antigen (PSMA) appears to be promising in patients with high-grade glioma. This study investigated [177Lu]Lu-PSMA therapy as an individual treatment approach with a focus on intratherapeutic dosimetry. Methods: Three patients were treated with a median of 6.03 GBq (interquartile range [IQR], 5.74-6.10) of [177Lu]Lu-PSMA. Intratherapeutic dosimetry was performed using a hybrid scenario with planar whole-body scintigraphy at 2, 24, and 48 h after treatment injection and SPECT/CT at 48 h after injection. Additive whole-body scintigraphy at 8 d after injection was performed on 1 patient. Results: The median doses were 0.56 Gy (IQR, 0.36-1.25 Gy) to tumor, 0.27 Gy (IQR, 0.16-0.57 Gy) to risk organs, 2.13 Gy (IQR, 1.55-2.89 Gy) to kidneys, and 0.76 Gy (IQR, 0.70-1.20 Gy) to salivary glands. Whole-body exposure was 0.11 Gy (IQR, 0.06-0.18 Gy). Conclusion: Because the intratherapeutic tumor dose is lower than that used in external radiation oncology, the effectiveness of treatment is questionable.

Prostate-specific Membrane Antigen–radioguided Surgery Facilitates Pelvic Lymph Node Dissection During Radical Prostatectomy for the Treatment of Locally Advanced Prostate Cancer with Regional Lymph Node Metastases

Lymph node metastases (LNMs) are common in intermediate- to high-risk prostate cancer (PC) and may be missed during extended pelvic lymph node dissection (ePLND). Here we report on the use of prostate-specific membrane antigen (PSMA)-radioguided surgery (RGS) during open radical prostatectomy (RP) with ePLND to resect locoregional LNMs identified on preoperative PSMA positron emission tomography (PET). Preoperative PSMA PET showed 78 LNMs in 35 patients undergoing RP with ePLND and RGS between January 2018 and June 2020. In 14 patients (40%), LNMs were located outside the ePLND template. RGS achieved resection of PSMA-positive LNMs in 33/35 patients (94%). On univariable analysis, lower metastatic burden with up to two PSMA-positive LNMs on preoperative PET was associated with better postoperative outcomes. Limitations include the retrospective analysis and the small sample size. RGS facilitates resection of PSMA-positive LNs in patients treated with RP. Our data indicate a favorable treatment outcome in patients with low metastatic LN burden on preoperative PSMA PET. Patient summaryWe investigated the use of radioactive guidance to remove lymph nodes affected by prostate cancer during surgical removal of the prostate. This approach can help to identify cancerous lymph nodes that might otherwise be missed and could lead to better survival outcomes.

Using PSMA imaging for prognostication in localized and advanced prostate cancer.

The use of prostate-specific membrane antigen (PSMA)-directed applications in modern prostate cancer management has evolved rapidly over the past few years, helping to establish new treatment pathways and provide further insights into prostate cancer biology. However, the prognostic implications of PSMA-PET have not been studied systematically, owing to rapid clinical implementation without long follow-up periods to determine intermediate-term and long-term oncological outcomes. Currently available data suggest that traditional prognostic factors and survival outcomes are associated with high PSMA expression (both according to immunohistochemistry and PET uptake) in men with localized and biochemically recurrent disease. Treatment with curative intent (primary and/or salvage) often fails when PSMA-positive metastases are present; however, the sensitivity of PSMA-PET in detecting all metastases is poor. Low PSMA-PET uptake in recurrent disease is a favourable prognostic factor; however, it can be associated with poor prognosis in conjunction with high 18F-fluorodeoxyglucose uptake in metastatic castration-resistant prostate cancer. Clinical trials embedding PSMA-PET for guiding management with reliable oncological outcomes are needed to support ongoing clinical use.

Pharmacological Optimization of PSMA-Based Radioligand Therapy.

Prostate cancer (PCa) is the most common malignancy in men of middle and older age. The standard treatment strategy for PCa ranges from active surveillance in low-grade, localized PCa to radical prostatectomy, external beam radiation therapy, hormonal treatment and chemotherapy. Recently, the use of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) for metastatic castration-resistant PCa has been approved. PSMA is predominantly, but not exclusively, expressed on PCa cells. Because of its high expression in PCa, PSMA is a promising target for diagnostics and therapy. To understand the currently used RLT, knowledge about pharmacokinetics (PK) and pharmacodynamics (PD) of the PSMA ligand and the PSMA protein itself is crucial. PK and PD properties of the ligand and its target determine the duration and extent of the effect. Knowledge on the concentration-time profile, the target affinity and target abundance may help to predict the effect of RLT. Increased specific binding of radioligands to PSMA on PCa cells may be associated with better treatment response, where nonspecific binding may increase the risk of toxicity in healthy organs. Optimization of the radioligand, as well as synergistic effects of concomitant agents and an improved dosing strategy, may lead to more individualized treatment and better overall survival.

PSMA Expression in Solid Tumors beyond the Prostate Gland: Ready for Theranostic Applications?

In the past decades, the expanding use of prostate-specific membrane antigen (PSMA) imaging for prostate cancer has led to the incidental detection of a lot of extra-prostatic malignancies showing an increased uptake of PSMA. Due to these incidental findings, the increasing amount of immunohistochemistry studies and the deeper knowledge of the mechanisms of expression of this antigen, it is now clear that "PSMA" is a misnomer, since it is not specific to the prostate gland. Nevertheless, this lack of specificity could represent an interesting opportunity to bring new insights on the biology of PSMA and its sites of expression to image and treat new conditions, particularly several cancers. In this review, we will describe the main extra-prostatic cancers that exhibit PSMA expression and that can be studied with PSMA-based positron emission tomography-computed tomography (PET/CT) as an additional or alternative tool to conventional imaging. In particular, we will focus on cancers in which a radioligand therapy with 177lutetium has been attempted, aiming to provide an overview of the possible future theragnostic applications of PSMA.

Association of True Positivity with Serum Prostate-Specific Antigen Levels and Other Clinical Factors in Indeterminate PSMA-RADS-3A Lesions Identified on 18F-DCFPyL PET/CT Scans.

The use of prostate-specific membrane antigen targeted PET imaging for the evaluation of prostate cancer has increased significantly in the last couple of decades. When evaluating these imaging findings based on the PSMA reporting and data system version 1.0, which categorize lesions based on their likelihood of prostate cancer involvement, PSMA-RADS-3A lesions are commonly seen, which are indeterminate for the presence of disease. A total of 28 patients with 171 PSMA-RADS-3A lesions on 18F-DCFPyL PET/CT scans from June 2016 to May 2017 who had follow-up cross-sectional imaging over time were included in this study. The PSA levels of patients with PSMA-RADS-3A lesions were categorized into four groups, 0-0.2, 0.2-1, 1-2, and >2 ng/mL. The pre-operative Gleason score of these patients was categorized into two groups, Gleason score < 7 or ≥7. The median age for these patients was 72.5 years (range 59-81). The median PSA value for patients with positive lesions was significantly higher than those with negative lesions (5.8 ng/mL vs. 0.2 ng/mL, p < 0.0001). The lesion positivity rate was significantly higher in patients with PSA > 1 ng/mL (18.2% vs. 81.9%, p < 0.001). On ROC analysis, the highest classification accuracy was seen at PSA ≥ 0.6 ng/mL of 80.12% (95% CI = 73.69-86.16%), and the area under the curve was 71.32% (95% CI = 61.9-80.7%, p < 0.0001). A total of 96.4% (108/112) of patients with positive lesions and 86.4% (51/59) of patients with negative lesions had a PSMA-RADS-4/5 lymph node on the initial 18F-DCFPyL PET/CT scan (p = 0.02). In patients with a Gleason score ≥ 7, the presence of positive PSMA-RADS-3A lesions was higher, compared to negative PSMA-RADS-3A lesions (p = 0.049). Higher PSA levels in patients with PSMA-RADS-3A lesions can point towards the presence of true positivity. PSA levels may be considered in deciding whether to call an indeterminate lesion on PSMA PET.

PSMA PET/CT in Renal Cell Carcinoma: An Overview of Current Literature.

Although the vast majority of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging occurs in the field of prostate cancer, PSMA is also highly expressed on the cell surface of the microvasculature of several other solid tumors, including renal cell carcinoma (RCC). This makes it a potentially interesting imaging target for the staging and monitoring of RCC. The objective of this review is to provide an overview of the current evidence regarding the use of PSMA PET/Computed Tomography in RCC patients.

Utilidad de los radioligandos PSMA en el diagnóstico y tratamiento del carcinoma de próstata

Prostate cancer (PC) is the most common tumor in men in the West and the fifth leading cause of cancer-related death. The use of prostate-specific membrane antigen (PSMA) radioligands has represented an important advance in both in the diagnosis by positron emission tomography (PET) molecular imaging and the treatment of advanced stages of the disease. This article reviews the contribution of PET studies with PSMA radioligands in the initial staging, tumor detection in biochemical recurrence (elevation of PSA) after treatment with curative intent, and in the more advanced stages of the disease (castration-resistant PC [CRPC]). The contribution of PSMA radioligand therapy in CRPC patients who progress to standard therapy is also analyzed.

Prostate-Specific Membrane Antigen (PSMA) Theranostics for Treatment of Oligometastatic Prostate Cancer.

Theranostics, a combination of therapy and diagnostics, is a field of personalized medicine involving the use of the same or similar radiopharmaceutical agents for the diagnosis and treatment of patients. Prostate-specific membrane antigen (PSMA) is a promising theranostic target for the treatment of prostate cancers. Diagnostic PSMA radiopharmaceuticals are currently used for staging and diagnosis of prostate cancers, and imaging can predict response to therapeutic PSMA radiopharmaceuticals. While mainly used in the setting of metastatic, castrate-resistant disease, clinical trials are investigating the use of PSMA-based therapy at earlier stages, including in hormone-sensitive or hormone-naïve prostate cancers, and in oligometastatic prostate cancers. This review explores the use of PSMA as a theranostic target and investigates the potential use of PSMA in earlier stage disease, including hormone-sensitive metastatic prostate cancer, and oligometastatic prostate cancer.

Comparison between 177Lu-iPSMA and 225Ac-iPSMA dosimetry at a cellular level in an animal bone metastasis model

The recent use of prostate-specific membrane antigen as a biological target have improved the theragnostic approach to prostate and other types of cancer. Radiopharmaceuticals based on PSMA inhibitors radiolabeled with beta emitters as Lutetium-177 have demonstrated remarkable efficacy and safety, however, their clinical evaluation have also shown that therapeutic response of bone located metastases is poorer than that presented by soft tissue lesions. These observations conducted to the development and study at different levels of PSMA-targeting alpha-particle therapy exhibiting effective and promising antitumor activity. However, some aspects of the use of alpha emitters such as cellular dosimetry should be considered before applying them safely. The aim of the present work was to compare and calculate the absorbed dose of 177Lu-iPSMA and 225Ac-iPSMA using an animal bone metastasis model and experimental data obtained from cellular fractionation. The number of disintegrations and the dose factors for the theragnostic iPSMA pair, molecule that can be radiolabeled with 177Lu or 225Ac, were determined based on MIRD methodology, and used to calculate the absorbed dose to cell nucleus. A five times difference between 225Ac-iPSMA and 177Lu-iPSMA average dose rate to the tumor was calculated, being 2.3 ± 0.037 for the first and 0.5 ± 0.018 Gy for the second, both for each activity unit (MBq) administered.

Correlation of Lesional Uptake Parameters and Ratios with miPSMA Score and Estimating Normal Physiologic Concentration: An Exploratory Analysis in Metastatic Castration-Resistant Prostatic Carcinoma Patients with 68Ga-PSMA-11 PET/CT.

The use of prostate-specific membrane antigen (PSMA)-based PET/CT has grown rapidly in recent years. This study estimated lesional uptake, normal physiologic concentrations, and temporal variation on delayed PET/CT of 68Ga-PSMA-11 across different molecular imaging PSMA (miPSMA) expression scores in patients with metastatic castration-resistant prostatic carcinoma. Methods: We retrospectively studied 50 patients who were evaluated for 177Lu-PSMA-targeted radioligand therapy and underwent 68Ga-PSMA-11 PET/CT to determine disease status. Their mean age was 67.5 ± 8 y (52-84 y), and their average serum prostate-specific antigen level was 401 ± 1,353 ng/mL (0.098-9,235.13 ng/mL) at the time of scanning. They underwent standard 68Ga-PSMA-11 PET/CT an average of 65 min after injection (60-90 min). Tumors (n = 50) were correlated with miPSMA expression score and uptake. Physiologic tracer distribution was estimated by placing a volume of interest 1 cm in diameter for smaller organs (submandibular, parotid, lacrimal, and tubarial glands; renal cortices; blood pool; and bowel) and 3 cm for larger organs (liver and spleen). SUVmax and SUVmean were estimated for each region. Tumor-to-spleen (T/S), tumor-to-liver (T/L), and tumor-to-parotid (T/P) ratios were calculated for each lesion. For 16 patients who underwent a delayed scan an average of 135 min after injection (120-150 min), additional analysis evaluated the effect of the delay. Results: Uptake was maximal in renal cortices, followed by salivary glands, bowel, spleen, liver, lacrimal glands, and blood pool. SUVmax averaged 37.7 ± 22.1 for renal cortices, 15.4 ± 7.3 for submandibular glands, 14.4 ± 7.1 for parotid glands, 9.4 ± 4.9 for spleen, 6.2 ± 3.7 for lacrimal glands, 5.9 ± 2.3 for liver, 5.3 ± 1.41 for tubarial glands, 13.8 ± 7.6 for bowel, and 2.4 ± 1.9 for blood pool. SUVmax averaged 10.33 ± 3.27 (6.46-17) for miPSMA expression score 2 and 38.21 ± 25.9 (7.68-119.08) for score 3. T/S and T/P ratios averaged 1.21 ± 0.44 (0.48-2.04) and 0.6 ± 0.18 (0.39-0.87), respectively, for score 2 and 5.05 ± 4.46 (1.25-20.89) and 3.15 ± 2.09 (1.06-9.45), respectively, for score 3. SUVmax for score 3 lesions averaged 18.85, which increased significantly to 26.24 on delayed imaging (P = 0.0001). However, T/L, T/S, and T/P ratios did not significantly change. Temporal variation in normal organs showed SUVmax to increase significantly on delayed scans for salivary (submandibular and parotid) and lacrimal glands and renal cortices, whereas SUVmean increased significantly for spleen; liver; and parotid, tubarial, and lacrimal glands and insignificantly for other organs. Conclusion: These data form a basis for a proposed consensus on standard reference ranges for quantitative 68Ga-PSMA-11 PET/CT. The temporal variations should be kept in mind for delayed acquisitions; T/S, T/L, and T/P ratios might serve as better markers for such scenarios.

More Than Meets the Eye: Scientific Rationale behind Molecular Imaging and Therapeutic Targeting of Prostate-Specific Membrane Antigen (PSMA) in Metastatic Prostate Cancer and Beyond.

Simple SummaryProstate-specific membrane antigen (PSMA) is a transmembrane protein that is overexpressed in prostate cancer and correlates with the aggressiveness of the disease. PSMA is a promising target for imaging and therapeutics in prostate cancer patients validated in prospective trials. However, the role of PSMA in prostate cancer progression is poorly understood. In this review, we discuss the biology and scientific rationale behind the use of PSMA and other targets in the detection and theranostics of metastatic prostate cancer.Prostate cancer is the second most common cancer type in men globally. Although the prognosis for localized prostate cancer is good, no curative treatments are available for metastatic disease. Better diagnostic methods could help target therapies and improve the outcome. Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that is overexpressed on malignant prostate tumor cells and correlates with the aggressiveness of the disease. PSMA is a clinically validated target for positron emission tomography (PET) imaging-based diagnostics in prostate cancer, and during recent years several therapeutics have been developed based on PSMA expression and activity. The expression of PSMA in prostate cancer can be very heterogeneous and some metastases are negative for PSMA. Determinants that dictate clinical responses to PSMA-targeting therapeutics are not well known. Moreover, it is not clear how to manipulate PSMA expression for therapeutic purposes and develop rational treatment combinations. A deeper understanding of the biology behind the use of PSMA would help the development of theranostics with radiolabeled compounds and other PSMA-based therapeutic approaches. Along with PSMA several other targets have also been evaluated or are currently under investigation in preclinical or clinical settings in prostate cancer. Here we critically elaborate the biology and scientific rationale behind the use of PSMA and other targets in the detection and therapeutic targeting of metastatic prostate cancer.

Diagnostic Role of 18F-PSMA-1007 PET/CT in Prostate Cancer Staging: A Systematic Review.

Background: The use of prostate-specific membrane antigen (PSMA)-targeted agents for staging prostate cancer (PCa) patients using positron emission tomography/computed tomography (PET/CT) is increasing worldwide. We performed a systematic review on the role of 18F-PSMA-1007 PET/CT in PCa staging to provide evidence-based data in this setting. Methods: A comprehensive computer literature search of PubMed/MEDLINE and Cochrane Library databases for studies using 18F-PSMA-1007 PET/CT in PCa staging was performed until 31 December 2020. Eligible articles were selected and relevant information was extracted from the original articles by two authors independently. Results: Eight articles (369 patients) evaluating the role of 18F-PSMA-1007 PET/CT in PCa staging were selected. These studies were quite heterogeneous, but, overall, they demonstrated a good diagnostic accuracy of 18F-PSMA-1007 PET/CT in detecting PCa lesions at staging. Overall, higher primary PCa aggressiveness was associated with higher 18F-PSMA-1007 uptake. When compared with other radiological and scintigraphic imaging methods, 18F-PSMA-1007 PET/CT had superior sensitivity in detecting metastatic disease and the highest inter-reader agreement. 18F-PSMA-1007 PET/CT showed similar results in terms of diagnostic accuracy for PCa staging compared with PET/CT with other PSMA-targeted tracers. Dual imaging with multi-parametric magnetic resonance imaging and 18F-PSMA-1007 PET/CT may improve staging of primary PCa. Notably, 18F-PSMA-1007-PET/CT may detect metastatic disease in a significant number of patients with negative standard imaging. Conclusions: 18F-PSMA-1007 PET/CT demonstrated a good accuracy in PCa staging, with similar results compared with other PSMA-targeted radiopharmaceuticals. This method could substitute bone scintigraphy and conventional abdominal imaging for PCa staging. Prospective multicentric studies are needed to confirm these findings.

68Ga-PSMA-11 Positron Emission Tomography/Computed Tomography for Primary Lymph Node Staging Before Radical Prostatectomy: Central Review of Imaging and Comparison with Histopathology of Extended Lymphadenectomy

BackgroundResults from prospective trials have shown higher accuracy of prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET)/computed tomography (CT) in detection of lymph node metastasis (LNM) compared to conventional imaging. ObjectiveTo evaluate the accuracy of 68Ga-PSMA-11 PET/CT for LNM detection in patients undergoing radical prostatectomy (RP) and extended pelvic lymph node dissection (PLND). Design, setting, and participantsBetween June 2014 and November 2020, 96 patients with 68Ga-PSMA PET/CT for primary staging underwent RP and extended PLND. Outcome measurements and statistical analysisThe results from 68Ga-PSMA PET/CT were compared with histologic data from primary PLND in 96 patients. All 68Ga-PSMA PET/CT scans were centrally reviewed. Results and limitationsOf 96 patients, 15.6% (n = 15) harbored LNMs. The median prostate-specific antigen at 68Ga-PSMA PET/CT was 8.0 ng/ml (interquartile range 5.5–11.7). The majority of patients had intermediate- (52.1%) or high-risk disease (41.7%). Biopsy grade group 4 and 5 was present in 22.9% and 15.6%, respectively. The 68Ga-PSMA PET/CT scans identified eight of 15 patients (53.3%) as LN-positive (true positive). The calculated per-patient sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 68Ga-PSMA PET/CT in the detection of LNM were 53.3%, 98.8%, 88.9%, 92.0%, and 91.7%, respectively. The per-patient sensitivity and specificity in the detection of LNMs larger than 2 mm were 61.5% and 98.8%, respectively. The main limitation is the retrospective design of the study. Conclusions68Ga-PSMA PET/CT is accurate in lymph node staging and the results support its use for primary staging of prostate cancer. Patient summaryWe compared prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET)/computed tomography (CT) findings with histopathology results after extended lymph node dissection and showed that it is accurate in detecting lymph node metastases. Our results support the use of PSMA PET/CT for primary staging of prostate cancer.

Hybrid imaging in prostate cancer : Status quo and future applications

Recently, the use of prostate-specific membrane antigen (PSMA) tracers like 68Ga-PSMA-11 in positron emission tomography (PET) have shown promising results and are helping to improve care for patients with prostate cancer (PC). In the following we review the current literature on PSMA-ligand PET, in particular with regard to the currently increasing replacement of 68Ga-PSMA ligands by 18F-labeled PSMA ligands. PSMA-ligand PET is most frequently used for biochemical recurrence. Here, 68Ga-PSMA-11 PET/CT shows superior detection rates compared to conventional imaging modalities, especially in small, morphologically unsuspicious lesions, even at low PSA values. Furthermore, 68Ga-PSMA PET imaging seems to be an encouraging alternative for staging of high-risk patients, particularly in combination with multiparametric MRI. The use of PSMA-ligand PET has revolutionized PC imaging. Thus, PSMA-ligand PET is expected to play an even greater role in PC diagnostics in the future, especially as 18F-labeled PSMA ligands are now increasingly used. However, simultaneous image analysis of PET and CT as well as adifferentiated image evaluation (clinical context, knowledge of common pitfalls) is mandatory.

Prostate-specific membrane antigen for the surgical oncologist: interpreting expression beyond the prostate.

The use of prostate-specific membrane antigen (PSMA) radiotracer in positron emission tomography (PET) has been successfully incorporated into the clinical management of prostate cancer. However, PSMA tracer uptake is not limited to prostate cancer tissue. We reviewed studies exploring PSMA expression beyond the prostate gland using techniques of 68 Ga-PSMA PET imaging and immunohistochemistry. PSMA expression has been associated with a variety of solid tumours, and the vasculature associated with neoplastic disease, suggesting that this trans-membrane glycoprotein may be involved in the neovascularisation process in malignancy. These studies demonstrate the need for more research into the potential utility for 68 Ga-PSMA PET imaging in patients with non-prostatic cancers.