Synthesis of an I-123 analog of A-85380 and preliminary SPECT imaging of nicotinic receptors in baboon

A radiosynthetic method to prepare the nicotinic acetylcholine receptor radioligand ( S)-5-[ 123I]iodo-3-(2-azetidinylmethoxy)pyridine, 5-IA, has been developed. The two-step sequence produced [ 123I]-5-IA in high radiochemical yield (52%), high radiochemical purity (98%), and high specific radioactivities (>8,500 mCi/μmol). Preliminary single photon emission computed tomography studies with [ 123I]-5-IA in baboon demonstrated the appropriate regional localization for a high-affinity nicotinic radioprobe (thalamus > frontal cortex > cerebellum). Pretreatment with cytisine blocked [ 123I]-5-IA uptake in all brain regions (78–59% reduction), demonstrating the specificity of the radiotracer.