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

Abstract

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.