Development and Preliminary Evaluations of a NovelF-Labeled Tracer for Detection of BRAFMutant Status in Animal Models of Melanoma.

Abstract

The BRAFmutation is a well-established oncogenic driver, and several oral inhibitors have achieved clinical success. However, radiolabeled tracers for the non-invasive imaging of this mutation remain limited.-(2-Chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroquinazolin-6-yl)oxy)-5-fluorophenyl)propane-1-sulfonamide () is a novel oral inhibitor targeting BRAFwith high inhibitory potency. Here, we report the synthesis of its precursor and the radiosynthesis of itsF-labeled version, [F]LP-1 ([F]). The tracer exhibited nanomolar cellular binding affinity for BRAF-positive A375 melanoma cells (IC= 31.6 nM) and demonstrated selective uptake in tumor models with distinct BRAF mutation status. Blocking studies with the BRAF-selective inhibitor vemurafenib further confirmed its specific binding. Our findings highlight the potential of [F]LP-1 as a lead structure for the development of PET molecular tracers capable of detecting BRAFmutation status in vivo and support the development of next-generation radiotracers based on the scaffold.