Preoperative PET imaging and fluorescence-guided surgery of human glioblastoma using dual-labeled antibody targeting ETA receptors in a preclinical mouse model: A theranostic approach

Glioblastoma (GBM) poses significant challenges regarding complete tumor removal due to its heterogeneity and invasiveness, emphasizing the need for effective therapeutic options. In the last two decades, fluorescence-guided surgery (FGS), employing fluorophores such as 5-aminolevulinic acid (5-ALA) to enhance tumor delineation, has gained attraction among neurosurgeons. However, some low-grade tumors do not show any accumulation of the tracers, and the lack of patient stratification represents an important limitation. Since 2000, endothelin axis has been extensively investigated for its role in cancer progression. More specifically, our team has identified endothelin A receptors (ET_A), overexpressed in glioblastoma cancer stem cells, as a target of interest for GBM imaging. This study aims to evaluate the efficacy of a novel preclinical bimodal imaging agent, [⁸⁹Zr]Zr-axiRA63-MOMIP, as a theranostic approach to: i) detect ET_A⁺ cells in an orthotopic model of human GBM, ii) achieve complete tumoral resection.