title: Synthesis and evaluation of 3-¹²³I-iodo-5-[2-(S)-3-pyrrolinylmethoxy]-pyridine (niodene) as a potential nicotinic α4β2 receptor imaging agent.
abstract: Nicotinic acetylcholine receptors (nAChRs) are downregulated in disease conditions such as Alzheimer's and substance abuse. Presently, (123)I-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 (123)I-5-IA-85380, which may reduce scanning time and help in imaging studies. Binding affinity K(i) of niodene for rat brain α4β2 receptors in brain homogenate assays using (3)H-cytisine was 0.27 nM. Niodene, 10nM displaced >95% of (18)F-nifene bound to α4β2 receptors in rat brain slices. By using the iododestannylation method, (123)I-niodene was obtained in high radiochemical purity (>95%) but with low radiochemical yield (<5%) and low specific activity (∼100 Ci/mmol). Autoradiograms show (123)I-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 (123)I-niodene in higher radiochemical yields and higher specific activity of this potentially useful new SPECT imaging agent.
authors.affiliation: Preclinical Imaging, B140 Medical Sciences, Department of Radiological Sciences, University of California - Irvine, Irvine, CA 92697, United States.
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Pandey
authors.forename: Shawn
authors.initials: S
authors.lastname: Pan
authors.forename: Ritu
authors.initials: R
authors.lastname: Kant
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Kuruvilla
authors.forename: Min-Liang
authors.initials: ML
authors.lastname: Pan
authors.forename: Jogeshwar
authors.initials: J
authors.lastname: Mukherjee
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D003287:Contrast Media / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C581118:3-123I-iodo-5-(2-(S)-3-pyrrolinylmethoxy)-pyridine; D003287:Contrast Media; D011725:Pyridines; D011758:Pyrroles; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2