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

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 (13)N labelling strategies and tracers by adapting the multicomponent Hantzsch condensation reaction to prepare a library of (13)N-labelled 1,4-dihydropyridines from [(13)N]ammonia, including the widely-used drug nifedipine. This represents a key advance in (13)N PET radiochemistry, and will serve to underpin the renewed interest in clinical opportunities offered by short-lived PET tracers.