title: In vivo characterization of radioiodinated (+)-2-[4-(4-iodophenyl) piperidino] cyclohexanol as a potential sigma-1 receptor imaging agent.
abstract: In this study, the (+)-enantiomer of radioiodinated 2-[4-(4-iodophenyl)piperidino]cyclohexanol [(+)-[(125)I]-p-iodovesamicol] [(+)-[(125)I]pIV], which is reported to bind with high affinity to sigma-1 receptors in vitro, was tested for its usefulness in imaging sigma-1 receptors in the central nervous system (CNS) in vivo. In biodistribution studies, significant amounts (approximately 3% of the injected dose) of (+)-[(125)I]pIV accumulated in rat brain, and its retention was prolonged. In blocking studies, the accumulation of (+)-[(125)I]pIV in the rat brain was significantly reduced by the coadministration of sigma-ligands such as pentazocine (5.0 micromol), haloperidol (0.5 micromol) or SA4503 (0.5 micromol). The blocking effect of pentazocine (selective sigma-1 ligand) was similar to the blocking effects of SA4503 and haloperidol [nonselective sigma (sigma-1 and sigma-2) ligands]. Ex vivo autoradiography of the rat brain at 45 min following intravenous injection of (+)-[(125)I]pIV showed high localization in brain areas rich in sigma-1 receptors. Thus, the distribution of (+)-[(125)I]pIV was thought to bind to sigma-1 receptors in the CNS in vivo. These results indicate that radioiodinated (+)-pIV may have the potential to image sigma-1 receptors in vivo.
authors: Department of Biotracer Medicine, Kanazawa University, Kanazawa 920-8640, Japan.
authors: Nasima
authors: N
authors: Akhter
authors: Kazuhiro
authors: K
authors: Shiba
authors: Kazuma
authors: K
authors: Ogawa
authors: Seigo
authors: S
authors: Kinuya
authors: Kenichi
authors: K
authors: Nakajima
authors: Hirofumi
authors: H
authors: Mori
mesh_terms: D000818:Animals; D001345:Autoradiography; D001711:Biotransformation; D001921:Brain / Q000000981:diagnostic imaging; D002490:Central Nervous System / Q000000981:diagnostic imaging*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003511:Cyclohexanols / Q000737:chemistry; D006220:Haloperidol / Q000494:pharmacology; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D018697:Nootropic Agents / Q000494:pharmacology; D010423:Pentazocine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000737:chemistry; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013237:Stereoisomerism; D014018:Tissue Distribution; D000097605:Sigma-1 Receptor
chemical_list: D003511:Cyclohexanols; D006220:Haloperidol; D007457:Iodine Radioisotopes; D009292:Narcotic Antagonists; D018697:Nootropic Agents; D010423:Pentazocine; D010879:Piperazines; D010880:Piperidines; D019275:Radiopharmaceuticals; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C502476:2-(4-(4-iodophenyl) piperidino)cyclohexanol; C101789:SA 4503