5-(5-(6-[11C]methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin-2-yl)-1H-indole as a potential PET radioligand for imaging cerebral α7-nAChR in mice

The radiosynthesis and in vivo evaluation of 5-(5-(6-[11C]methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin-2-yl)-1H-indole [11C]rac-(1), a potential PET tracer for α7 nicotinic acetylcholine receptors (α7-nAChR), are described. Syntheses of the nonradioactive standard rac-1 and corresponding desmethyl precursor 7 were achieved in several reaction steps. Radiomethylation of 7 with [11C]CH3I afforded [11C]rac-1 in an average radiochemical yield of 30 ± 5% (n = 5) with high radiochemical purity and an average specific radioactivity of 444 ± 74 GBq/μmol (n = 5). The total synthesis time was 30 min from end-of-bombardment. Biodistribution studies in mice showed that [11C]rac-1 penetrates the blood-brain barrier and specifically labels neuronal α7-nAChRs.