Prostate-Specific Membrane Antigen as Target for Neuroimaging of Central Nervous System Tumors

Abstract

Introduction. Positron emission tomography (PET) imaging with prostate-specific membrane antigen- (PSMA-) binding tracers has been found incidentally to demonstrate uptake in CNS tumors. Following the encouraging findings of several such case reports, there is a growing interest in the potential application of PSMA-targeted PET imaging for diagnostics, theranostics, and monitoring of CNS tumors. This is a systematic literature review on PSMA-binding tracers in CNS tumors. Methods. A PubMed search was conducted, including preclinical and clinical reports. One hundred and twelve records were identified, and after screening, 56 were included in the final report. Results. Tissue studies demonstrated PSMA expression in tumor vascular endothelial cells, without expression in normal brain tissue, though the extent and intensity of staining varied by anti-PSMA antibody and methodology. Most included studies reported on gliomas, which showed strong PSMA ligand uptake and more favorable tumor to background ratios than other PET tracers. There are also case reports demonstrating PSMA ligand uptake in prostate cancer brain metastases, nonprostate cancer brain metastases, and meningiomas. We also review the properties of the various PSMA-binding radiotracers available. Therapeutic and theranostic applications of PSMA-binding tracers have been studied, including labeled alpha- and beta-ray emitting isotopes, as well as PSMA targeting in directing MRI-guided focused ultrasound. Conclusions. There is a potential application for PSMA-targeted PET in neuro-oncology as a combination of diagnostic and therapeutic use, as a theranostic modality for managing CNS tumors. Further research is needed regarding the mechanism(s) of PSMA expression in CNS tumors and its differential performance by tumor type.

Pharmacological Optimization of PSMA-Based Radioligand Therapy

“…PSMA is significantly overexpressed in most PCa cells (>90%) and its expression is even higher in high-grade, aggressive and dedifferentiated tumors [ 5 ]. In addition, PSMA is also expressed in other types of malignancies, among which are pancreatic, colorectal, gastric, central nerve system and renal cell carcinoma [ 6 , 7 , 8 , 9 ]. Because of its high expression in PCa, PSMA is a promising target for diagnostics and therapy (so called theranostics).…”

Diagnostic Accuracy of PET/CT or PET/MRI Using PSMA-Targeting Radiopharmaceuticals in High-Grade Gliomas: A Systematic Review and a Bivariate Meta-Analysis

“…Recent literature data and a growing body of evidence demonstrated that PSMA-targeted PET ameliorates staging and restaging of prostate cancer patients, changing the management in a significant percentage of cases [ 11 , 12 ]. Beyond prostate cancer, PSMA has been also demonstrated to be overexpressed by the neovasculature of many other solid tumors, including HGG [ 13 , 14 , 15 , 16 ]; this could be the rationale for using PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals in HGG or other solid tumors where [ 18 F]FDG PET has demonstrated low diagnostic accuracy [ 16 ]. Compared to other PET radiopharmaceuticals used for HGG, PSMA-targeting radiopharmaceuticals may evaluate a different tumor characteristic (tumor neoangiogenesis).…”

“…Several studies have used PSMA-targeting radiopharmaceuticals for PET imaging of HGG as reported in the literature [ 14 , 15 ]. The aim of this work is to perform a bivariate meta-analysis to calculate the diagnostic accuracy of PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals in patients with HGG in the following clinical settings: differential diagnosis among HGG and LGG before treatment and assessment of suspicious HGG recurrence after treatment.…”

Late Subacute Cerebral Hematoma Mimicking a Metastasis on PSMA PET/CT

“…Brain metastases from prostate cancer are rare, with a recent large cohort study of patients undergoing PSMA PET/CT yielding an incidence of 0.18% 1 . In addition to prostate cancer metastases, PSMA uptake in the brain has been described with primary brain tumors (such as glioblastoma 2 and meningioma 3 ), metastases from other primary malignancies, 4 infections, 5 acute and subacute cerebral infarction, 6,7 and intracranial hematomas 8–10 . Caution is therefore recommended before labeling areas of brain uptake as sites of metastatic disease, and MRI should always be obtained for further characterization.…”