Application of palladium-mediated (18)F-fluorination to PET radiotracer development: overcoming hurdles to translation.

Abstract

New chemistry methods for the synthesis of radiolabeled small molecules have the potential to impact clinical positron emission tomography (PET) imaging, if they can be successfully translated. However, progression of modern reactions from the stage of synthetic chemistry development to the preparation of radiotracer doses ready for use in human PET imaging is challenging and rare. Here we describe the process of and the successful translation of a modern palladium-mediated fluorination reaction to non-human primate (NHP) baboon PET imaging-an important milestone on the path to human PET imaging. The method, which transforms [(18)F]fluoride into an electrophilic fluorination reagent, provides access to aryl-(18)F bonds that would be challenging to synthesize via conventional radiochemistry methods.