Automated Radiochemical Synthesis of [ ¹⁸F]3F4AP: A Novel PET Tracer for Imaging Demyelinating Diseases

Abstract

3-[ ¹⁸F]fluoro-4-aminopyridine, [ ¹⁸F]3F4AP, is a radiofluorinated analog of the FDA-approved drug for multiple sclerosis 4-aminopyridine (4AP). This compound is currently under investigation as a PET tracer for demyelination. We recently described a novel chemical reaction to produce metafluorinated pyridines consisting of direct fluorination of a pyridine N-oxide and the utilization of this reaction for the radiochemical synthesis of [ ¹⁸F]3F4AP. In this article, we demonstrate how to produce this tracer using an automated synthesizer and an in-house made flow hydrogenation reactor. We also show the standard quality control procedures performed before releasing the radiotracer for preclinical animal imaging studies. This semi-automated procedure may serve as the basis for future production of [ ¹⁸F]3F4AP for clinical studies.