Synthesis and evaluation of 3-¹²³I-iodo-5-[2-(S)-3-pyrrolinylmethoxy]-pyridine (niodene) as a potential nicotinic α4β2 receptor imaging agent.

Nicotinic acetylcholine receptors (nAChRs) are downregulated in disease conditions such as Alzheimer’s and substance abuse. Presently, 123I-5-IA-85380 is used in human studies and requires over 6h of scanning time, thus increases patient discomfort. We have designed and synthesized 3-iodo-5-[2-(S)-3-pyrrolinylmethoxy]pyridine (niodene) with the aim to have faster binding kinetics compared to 123I-5-IA-85380, which may reduce scanning time and help in imaging studies. Binding affinity Ki of niodene for rat brain α4β2 receptors in brain homogenate assays using 3H-cytisine was 0.27nM. Niodene, 10nM displaced >95% of 18F-nifene bound to α4β2 receptors in rat brain slices. By using the iododestannylation method, 123I-niodene was obtained in high radiochemical purity (>95%) but with low radiochemical yield (<5%) and low specific activity (∼100Ci/mmol). Autoradiograms show 123I-niodene localized in the thalamus and cortex, which was displaced by nicotine (thalamus to cerebellum ratio=4; cortex to cerebellum ratio=1.6). Methods of radioiodination need to be further evaluated in order to obtain 123I-niodene in higher radiochemical yields and higher specific activity of this potentially useful new SPECT imaging agent.