Synthesis and evaluation of [125I]I-TSA as a brain nicotinic acetylcholine receptor alpha7 subtype imaging agent

Nuclear Medicine and Biology
Mikako OgawaYasuhiro Magata

Abstract

Some in vitro investigations have suggested that the nicotinic acetylcholine receptor (nAChR) alpha7 subtype is implicated in Alzheimer's disease, schizophrenia and others. Recently, we developed (R)-3'-(5-bromothiophen-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-[1',3']oxazolidin]-2'-one (Br-TSA), which has a high affinity and selectivity for alpha7 nAChRs. Therefore we synthesized (R)-3'-(5-[125I]iodothiophen-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-[1',3']oxazolidin]-2'-one ([125I]I-TSA) and evaluated its potential for the in vivo detection of alpha7 nAChR in brain. In vitro binding affinity of I-TSA was measured in rat brain homogenates. Radioiodination was accomplished by a Br-I exchange reaction. Biodistribution studies were undertaken in mice by tail vein injection of [(125)I]I-TSA. In vivo receptor blocking studies were carried out by treating mice with methyllycaconitine (MLA; 5 nmol/5 mul, i.c.v.) or nonradioactive I-TSA (50 micromol/kg, i.v.). I-TSA exhibited a high affinity and selectivity for the alpha7 nAChR (K(i) for alpha7 nAChR = 0.54 nM). Initial uptake in the brain was high (4.42 %dose/g at 5 min), and the clearance of radioactivity was relatively slow in the hippocampus (alpha7 nAChR-rich region) and was rath...Continue Reading

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Citations

Jan 13, 2009·European Journal of Nuclear Medicine and Molecular Imaging·Winnie Deuther-ConradPeter Brust
Jul 22, 2020·Autism Research : Official Journal of the International Society for Autism Research·Hafiz M MahmoodShakir D AlSharari
Feb 14, 2007·ChemMedChem·M Novella RomanelliFulvio Gualtieri
Mar 30, 2010·Nuclear Medicine and Biology·Mikako OgawaYasuhiro Magata

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