Automated radiosynthesis and preclinical imaging of a novel [18F]fluorolidocaine analogue via sequential C–H radiolabelling†

Abstract

The most prominent myocardial voltage-gated sodium channel, Na_V1.5, is a major drug target for treating cardiovascular disease. However, treatment determination and therapeutic development are complicated partly by an inadequate understanding of how the density of SCN5A, the gene that encodes Na_V1.5, relates to treatment response and disease prognosis. To address these challenges, imaging agents derived from Na_V1.5 blocking therapeutics have been employed in positron emission tomography (PET) imaging to infer how SCN5A expression relates to human disease in vivo. Herein, we describe the preparation of a novel fluorine-18 labelled analogue of lidocaine, a known Na_V1.5 inhibitor, and compare this agent to a previously described analogue. Evidence from rodent and non-human primate PET imaging experiments suggests that the imaging utility of these agents may be limited by rapid metabolism and clearance.