Synthesis And Evaluation Of 3-I-123-Iodo-5-[2-(S)-3-Pyrrolinylmethoxy]-Pyridine (Niodene) As A Potential Nicotinic Alpha 4 Beta 2 Receptor Imaging Agent

Nicotinic acetylcholine receptors (nAChRs) are downregulated in disease conditions such as Alzheimer's and substance abuse. Presently, I-123-5-IA-85380 is used in human studies and requires over 6 h 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 I-123-5-IA-85380, which may reduce scanning time and help in imaging studies. Binding affinity K-i of niodene for rat brain alpha 4 beta 2 receptors in brain homogenate assays using H-3-cytisine was 0.27 nM. Niodene, 10 nM displaced >95% of F-18-nifene bound to alpha 4 beta 2 receptors in rat brain slices. By using the iododestannylation method, I-123-niodene was obtained in high radiochemical purity (>95%) but with low radiochemical yield (<5%) and low specific activity (similar to 100 Ci/mmol). Autoradiograms show I-123-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 I-123-niodene in higher radiochemical yields and higher specific activity of this potentially useful new SPECT imaging agent. (C) 2012 Elsevier Ltd. All rights reserved.