Radiosynthesis of [ 11C]BBAC and [ 11C]BBPC as potential PET tracers for orexin2 receptors

摘要

Radiosynthesis of [N-methyl- 11C](S)-N-([1,1′-biphenyl]-2- yl)-1-(2-((1-methyl-1H-benzo[d]imidazol-2-yl)thio)acetyl)pyrrolidine-2- carboxamide ([ 11C]BBAC or [ 11C]3) and [N-methyl- 11C] (S)-N-([1,1′-biphenyl]-2-yl)-1-(3-(1-methyl-1H-benzo[d] imidazol-2-yl)propanoyl)pyrrolidine-2-carboxamide ([ 11C]BBPC or [ 11C]-4), two potential PET tracers for orexin2 receptors are described. Syntheses of non-radioactive standards 3, 4 and corresponding desmethyl precursors 1, 2 were achieved from common intermediate (S)-2-([1,1′-biphenyl]-2-yl)-1-(pyrrolidin-2-yl)ethanone. Methylation using [ 11C]CH 3OTf in the presence of base in acetone afforded [ 11C]3 and [ 11C]4 in 30 ± 5% yield (EOS) with 99 % radiochemical purities with a specific activity ranged from 2.5 ± 0.5 Ci/μmol (EOB). The log P of [ 11C]3 and [ 11C]4 were determined as 3.4 and 2.8, respectively. The total synthesis time was 30 min from EOB. However, PET scans performed in a rhesus monkey did not show tracer retention or appropriate brain uptake. Hence [ 11C]3 and [ 11C]4 cannot be used as PET tracers for imaging orexin2 receptors.