This paper systematically evaluates the uptake kinetics and distribution characteristics of PSMA-targeted ligands in gliomas through PET-MRI imaging combined with multi-modal MRI techniques, providing crucial evidence for the application of PSMA-targeted therapy in glioma treatment.
Literature Overview
This article titled 'DOSIMETRY AND IMMUNOHISTOCHEMISTRY STUDY TO ESTABLISH RADIOLABELLED PSMA AS A POTENTIAL THERANOSTIC TARGET IN GLIOMA TREATMENT', published in the journal 'Neuro-Oncology', reviews and summarizes the potential role of PSMA in glioma therapy, including its expression in tumor vascular endothelium, kinetic features under PET-MRI imaging, and correlations with histopathology. The passage is coherent and logically structured, ending with a period in Chinese.
Background Knowledge
Gliomas, particularly glioblastomas (GBM), are among the most common malignant tumors in the central nervous system, with extremely poor prognosis and a median survival of only 15 months. Standard treatment options are limited, highlighting an urgent need for novel molecular targets and imaging techniques to guide personalized therapy. PSMA (prostate-specific membrane antigen), a transmembrane protein initially identified in prostate cancer, has recently been found to be highly expressed in neovasculature of various non-prostate tumors, particularly in glioma angiogenic regions. This provides new insights for glioma-targeted therapy. This study further explores PSMA expression profiles and its therapeutic potential in gliomas using dynamic PET-MRI imaging combined with immunohistochemical analysis, offering foundational data for future radioligand therapies (e.g., [177Lu]PSMA).
Research Methods and Experiments
Three glioma patients underwent [68Ga]PSMA PET-MRI scans with dynamic imaging lasting 4.5 hours to assess ligand uptake kinetics. Static 15-minute scans were reconstructed at 60-75 minutes post-injection to evaluate uptake and tumor/background ratios (TBR). Multi-modal MRI images, including T1-weighted, FLAIR, perfusion, and permeability parameters, were acquired for co-localization analysis with PET signals. Intraoperative tumor biopsies were performed in selected regions, followed by PSMA immunohistochemistry (IHC) staining to validate consistency between PET signals and protein expression.
Key Conclusions and Perspectives
Research Significance and Prospects
This study establishes the feasibility of PSMA-targeted PET-MRI imaging in gliomas while revealing high expression in non-enhancing regions, expanding its application for tumor heterogeneity assessment. Future [177Lu]PSMA radioligand therapy may emerge as a novel glioma treatment approach. Additionally, PET combined with multi-modal MRI could provide molecular stratification and personalized treatment basis for gliomas, holding significant clinical translational potential.
Conclusion
This study systematically assessed PSMA's potential as a therapeutic and imaging target in gliomas. Through [68Ga]PSMA PET-MRI dynamic imaging, the authors identified stable PSMA expression in tumor neovascular regions, particularly in non-Gd-enhancing areas, suggesting continued targeting capability in regions invisible to conventional MRI. Furthermore, PSMA expression correlates with immunohistochemistry and MRI perfusion parameters, supporting its role as a biomarker for glioma microenvironment. Radiation dosimetry calculations for [177Lu]PSMA revealed safe-range delivery, providing theoretical support for subsequent clinical applications. These findings establish a solid preclinical foundation for PSMA-targeted glioma therapy and demonstrate promising prospects in neuro-oncology applications.
