The Hantzsch reaction for nitrogen-13 PET: preparation of [13N]nifedipine and derivatives

Abstract

Nitrogen-13 is an attractive but under-used PET radionuclide for labelling molecules of biological and pharmaceutical interest, complementing other PET radionuclides. Its short half-life (t_1/2 = 9.97 min) imposes synthetic challenges, but we have expanded the hitherto limited pool of ¹³N labelling strategies and tracers by adapting the multicomponent Hantzsch condensation reaction to prepare a library of ¹³N-labelled 1,4-dihydropyridines from [¹³N]ammonia, including the widely-used drug nifedipine. This represents a key advance in ¹³N PET radiochemistry, and will serve to underpin the renewed interest in clinical opportunities offered by short-lived PET tracers.