title: Regional brain imaging of vesicular acetylcholine transporter using o-[125 I]iodo-trans-decalinvesamicol as a new potential imaging probe.
abstract: In this study, the regional rat brain distribution of radioiodinated o-iodo-trans-decalinvesamicol ([(125) I]OIDV) was determined in vivo to evaluate its potential as a single-photon emission computed tomography (SPECT) imaging probe for vesicular acetylcholine transporter (VAChT). Following intravenous injection, [(125) I]OIDV passed freely across the blood-brain barrier and accumulated in rat brain. The accumulation of [(125) I]OIDV in rat brain was significantly reduced by coadministration of (+/-)-vesamicol (0.125 µmol). In contrast, the coadministration of σ-receptor ligands, such as (+)-pentazocine (0.125 µmol) as a σ-1 receptor ligand and (+)-3-(3-hydroxyphenyl)-N-propylpiperidine (0.125 µmol) as a σ-1 and σ-2 receptor ligands, barely affected the accumulation of [(125) I]OIDV in rat brain. These findings in vivo were corroborated by autoradiographic analysis ex vivo. The authors found that the tracer binds with pharmacological selectivity to VAChT in rat brain and predicted that it may likewise serve in translational SPECT imaging studies of this marker in the integrity of cholinergic innervations.
authors.affiliation: Division of Tracer Kinetics, Advanced Science Research Center, Kanazawa University, Kanazawa, Ishikawa, 920-8640, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kozaka
authors.forename: Izumi
authors.initials: I
authors.lastname: Uno
authors.forename: Yoji
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Daisuke
authors.initials: D
authors.lastname: Miwa
authors.forename: Mohammad
authors.initials: M
authors.lastname: Anwar-Ul Azim
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ogawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shiba
mesh_terms: D000818:Animals; D001345:Autoradiography; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D007457:Iodine Radioisotopes / Q000097:blood / Q000493:pharmacokinetics; D008024:Ligands; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D010423:Pentazocine / Q000494:pharmacology; D010880:Piperidines / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism*; D000097605:Sigma-1 Receptor
chemical_list: D007457:Iodine Radioisotopes; D008024:Ligands; D009292:Narcotic Antagonists; D010423:Pentazocine; D010880:Piperidines; D017480:Receptors, sigma; D050494:Vesicular Acetylcholine Transport Proteins; D000097605:Sigma-1 Receptor; C493461:Slc18a3 protein, rat; C578221:o-iodo-trans-decalinvesamicol; C106107:sigma-2 receptor; C006189:vesamicol; C026539:preclamol
keywords: autoradiography; imaging probe; in vivo; vesamicol analogs; vesicular acetylcholine transporter