Synthesis of the possible receptor ligand [131I]-3-iodo-cytisine for in vivo imaging of the nAChReceptor

In-vivo labeling of the nicotinic acetylcholine receptors (nAChRs) could be a useful tool for early diagnosis and evaluating therapies of neurodegenerative disorders. Although central nAChRs contribute to a variety of brain functions, relatively few data are available on their physiological functions and their potential role in neurological diseases. No data have yet been available on the regulation of nAChRs in the disease process of Alzheimer's disease or other neurodegenerative disorders in living patients. 2-[18F]-A85380 is the first radiotracer to visualize the distribution of nAChR in human brain in vivo. This PET ligand has a high affinity and subtype selectivity for α4β2 nAchR. A reduction of different nAChR subtypes has been reported in post-mortem brains of patients with Alzheimer's disease (AD), Parkinson's disease (PD) and dementia with Lewy bodies (DLB). 3-Iodo-cytisine displays a high affinity for neuronal nAChRs and subtype selectivity for α4β2 and thus for the radiolabeled analog a high potential can be expected for its clinical use in the diagnostic of neurodegenerative disorders. Here, we report on an optimized labeling of cytisine with iodine-131 by electrophilic substitution. (orig.)