Role of CXCR4 PET Imaging for the Evaluation of Gliomas: A Comprehensive Literature Review
Francesco Dondi, Pietro Bellini, Michela Cossandi, Roberto Rinaldi, Luca Camoni, Francesca Tomasoni, Massimo Statuto, Gian Luca Viganò, Francesco BertagnaC-X-C chemokine receptor type 4 (CXCR4)-targeted positron emission tomography (PET) radiotracers have recently emerged as promising molecular imaging tools for glioma evaluation because of their negligible physiological uptake in normal brain tissue and their ability to non-invasively assess CXCR4 expression. This narrative review summarizes the current evidence regarding their clinical applications in glioma imaging. a literature review was performed to identify clinical studies investigating CXCR4-targeted PET in glioma patients. The available evidence, although limited and heterogeneous, indicates that CXCR4-targeted PET tracers can provide high lesion-to-background contrast because of their minimal physiological uptake in normal brain tissue. Tracer uptake tends to be higher in high-grade gliomas, although correlations with histopathological CXCR4 expression and established prognostic biomarkers have been inconsistent. Preliminary studies have explored potential applications in tumor visualization, differentiation of recurrence from treatment-related changes, distinction between glioblastoma and primary central nervous system lymphoma, treatment response assessment, and radiotherapy planning. These findings require validation in larger prospective multicenter cohorts. CXCR4-targeted PET is an emerging molecular imaging approach that may provide complementary information in glioma assessment. However, the available evidence remains preliminary, and larger prospective multicenter studies are required to validate its diagnostic and clinical utility, standardize imaging and quantification protocols, and determine its role in routine neuro-oncological practice.