The BRAFV600E mutation 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. N-(2-Chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroquinazolin-6-yl)oxy)-5-fluorophenyl)propane-1-sulfonamide (74) is a novel oral inhibitor targeting BRAFV600E with high inhibitory potency. Here, we report the synthesis of its precursor and the radiosynthesis of its 18F-labeled version, 18FLP-1 (18F74). The tracer exhibited nanomolar cellular binding affinity for BRAFV600E-positive A375 melanoma cells (IC50 = 31.6 nM) and demonstrated selective uptake in tumor models with distinct BRAF mutation status. Blocking studies with the BRAFV600E-selective inhibitor vemurafenib further confirmed its specific binding. Our findings highlight the potential of 18FLP-1 as a lead structure for the development of PET molecular tracers capable of detecting BRAFV600E mutation status in vivo and support the development of next-generation radiotracers based on the scaffold.
Guo et al. (Fri,) studied this question.