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.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Pandey SK,Pan S,Kant R,Kuruvilla SA,Pan ML,Mukherjee Jdoi
10.1016/j.bmcl.2012.10.012subject
Has Abstractpub_date
2012-12-15 00:00:00pages
7610-4issue
24eissn
0960-894Xissn
1464-3405pii
S0960-894X(12)01279-6journal_volume
22pub_type
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