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

## TL;DR

A new fluorine-18 labelled lidocaine drug is developed for PET imaging to study heart sodium channels, but it is quickly broken down in the body.

## Contribution

A novel [18F]fluorolidocaine analogue was synthesized using sequential C–H radiolabelling for PET imaging.

## Key findings

- The new [18F]fluorolidocaine analogue was successfully prepared via Ir/Cu C–H radiofluorination.
- Preclinical PET imaging showed rapid metabolism and clearance of the new imaging agent in rodents and non-human primates.
- The imaging utility of the agent may be limited due to its fast metabolic breakdown.

## Abstract

The most prominent myocardial voltage-gated sodium channel, NaV1.5, 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 NaV1.5, relates to treatment response and disease prognosis. To address these challenges, imaging agents derived from NaV1.5 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 NaV1.5 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.

A new fluorine-18-labelled lidocaine analogue has been successfully prepared using sequential Ir/Cu C–H radiofluorination. Preclinical PET studies indicate that these imaging agents undergo rapid metabolism and clearance.