Integrating Positron Emission Tomography (PET) Imaging of Prostate Specific Membrane Antigen (PSMA) to Monitor the Efficacy of Radiation Therapy in a Glioblastoma Murine Model

Abstract

Glioblastoma multiforme (GBM) stands out as one of the most aggressive types of cancers with a poor overall survival. Its pronounced molecular heterogeneity contributes to the challenge of treatment-resistance, and novel diagnostic and targeted therapeutic strategies are urgently needed. Prostate specific membrane antigen (PSMA) has emerged as a promising theranostic target in GBM, due to its reported selective expression in tumor-associated neo-vasculature.

In this study, we utilized dynamic PET imaging with the radiotracer [68Ga]Ga-PSMA-617 in a murine GBM model to investigate PSMA dynamics and its relevance to radiotherapy. Ionizing radiation was applied directly to the tumor in a single low dose of 3 Gy before PET/MRI was performed. To validate in vivo findings, western blot and immunohistochemistry analyses were conducted.

In vivo imaging indicated that ionizing radiation did not increase PSMA expression, contrary to western blot results that showed a radiation-induced upregulation of PSMA, including detectable levels of PSMA in healthy brain tissue. Immunohistochemistry further revealed specific localization of PSMA to the endothelial cells of tumor-associated vasculature in human GBM tissue, a pattern that was not observed in the murine tissue. These findings highlight the complexity of PSMA dynamics and underscore the importance of further research to validate its potential as a theranostic target, specifically in the context of radiation therapy.