VMT02 PET/CT imaging precisely detects melanoma in mouse models and patients by targeting MC1R

Accurate and early diagnosis of melanoma, a highly aggressive form of skin cancer, is critical for improving patient outcomes. Current diagnostic methods often lack the specificity or sensitivity required for early-stage detection or precise staging. The melanocortin-1 receptor (MC1R) presents an attractive target because it is significantly overexpressed in over 80% of melanoma cells, while maintaining low expression in normal tissues. This differential expression makes MC1R an ideal biomarker for targeted imaging and therapy, addressing a key gap in current melanoma diagnostics by offering a highly specific molecular target.

This chapter details the synthesis of VMT02, a 68Ga-labeled α-MSH peptide, and its application in PET/CT imaging. The methodology describes the production of a cyclized α-MSH peptide via an alternative click chemistry cyclization strategy, designed for enhanced MC1R binding kinetics. The study outlines comprehensive PET/CT imaging procedures applied in both mouse models and human patients. The primary objective was to demonstrate the probe's utility for visualizing melanoma lesions by exploiting the specific and high-affinity binding of VMT02 to MC1R on tumor cells, facilitating non-invasive diagnostic assessment.