title: A change of in vivo characteristics depending on specific activity of radioiodinated (+)-2-[4-(4-iodophenyl)piperidino]cyclohexanol [(+)-pIV] as a ligand for sigma receptor imaging.
abstract: The radioiodinated (+)-p-iodovesamicol [(+)-pIV], which shows a high binding affinity for sigma-1 (sigma-1) receptors, is prepared by an exchange reaction. The specific activity (SA) is fairly low and therefore is insufficient for clinical use. In this study, we prepared (+)-[(125)I]pIV with a high SA from tributylstannyl precursor and compared the in vivo characteristics between high and low SA by imaging sigma-1 receptors in the central nervous system. In the biodistribution study, a difference in brain accumulation was observed between the two methods. At 30 min postinjection, the brain accumulation (1.58%ID/g) of low SA [0.6-1.1 TBq/mmol (16-30 Ci/mmol)] (+)-[(125)I]pIV was higher than that (1.34%ID/g) of high SA [>88.8 TBq/mmol (>2400 Ci/mmol)] (+)-[(125)I]pIV. In the blocking study, the brain uptake of high SA (+)-[(125)I]pIV was reduced more significantly by the coadministration of sigma ligands such as pentazocine, haloperidol or SA4503 than that of low SA (+)-[(125)I]pIV. These results showed that nonspecific binding of high SA (+)-[(125)I]pIV in the brain was lower than that of low SA (+)-[(125)I]pIV, and high SA (+)-[(125)I]pIV bound more specifically to sigma-1 receptors in the brain than low SA (+)-[(125)I]pIV. In contrast, in the blood-binding study, high SA (+)-[(125)I]pIV (58.4%) bound to blood cells with higher affinity than low SA (+)-[(125)I]pIV (46.0%). In metabolite studies, blood metabolites of high SA (+)-[(125)I]pIV (57.3+/-3.5%) were higher than those of low SA (+)-[(125)I]pIV (45.5+/-4.1%) at 30 min postinjection. Higher SA may be apt to bind to blood cells with higher affinity and to be metabolized faster.
authors.affiliation: Department of Biotracer Medicine, Kanazawa University, Kanazawa 920-8640, Ishikawa, Japan.
authors.forename: Nasima
authors.initials: N
authors.lastname: Akhter
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shiba
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ogawa
authors.forename: Shiro
authors.initials: S
authors.lastname: Tsuji
authors.forename: Seigo
authors.initials: S
authors.lastname: Kinuya
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nakajima
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Mori
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003511:Cyclohexanols / Q000378:metabolism; D007457:Iodine Radioisotopes; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000378:metabolism; D011485:Protein Binding; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000378:metabolism*; D014018:Tissue Distribution; D000097605:Sigma-1 Receptor
chemical_list: D003511:Cyclohexanols; D007457:Iodine Radioisotopes; D010879:Piperazines; D010880:Piperidines; D019275:Radiopharmaceuticals; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C502476:2-(4-(4-iodophenyl) piperidino)cyclohexanol; C101789:SA 4503