title: In Vivo Differences between Two Optical Isomers of Radioiodinated o-iodo-trans-decalinvesamicol for Use as a Radioligand for the Vesicular Acetylcholine Transporter.
abstract: OBJECTIVE
  To develop a superior VAChT imaging probe for SPECT, radiolabeled (-)-OIDV and (+)-OIDV were isolated and investigated for differences in their binding affinity and selectivity to VAChT, as well as their in vivo activities.
  
  
  METHODS
  Radioiodinated o-iodo-trans-decalinvesamicol ([125I]OIDV) has a high binding affinity for vesicular acetylcholine transporter (VAChT) both in vitro and in vivo. Racemic [125I]OIDV was separated into its two optical isomers (-)-[125I]OIDV and (+)-[125I]OIDV by HPLC. To investigate VAChT binding affinity (Ki) of two OIDV isomers, in vitro binding assays were performed. In vivo biodistribution study of each [125I]OIDV isomer in blood, brain regions and major organs of rats was performed at 2,30 and 60 min post-injection. In vivo blocking study were performed to reveal the binding selectivity of two [125I]OIDV isomers to VAChT in vivo. Ex vivo autoradiography were performed to reveal the regional brain distribution of two [125I]OIDV isomers and (-)-[123I]OIDV for SPECT at 60 min postinjection.
  
  
  RESULTS
  VAChT binding affinity (Ki) of (-)-[125I]OIDV and (+)-[125I]OIDV was 22.1 nM and 79.0 nM, respectively. At 2 min post-injection, accumulation of (-)-[125I]OIDV was the same as that of (+)-[125I]OIDV. However, (+)-[125I]OIDV clearance from the brain was faster than (-)-[125I]OIDV. At 30 min post-injection, accumulation of (-)-[125I]OIDV (0.62 ± 0.10%ID/g) was higher than (+)-[125I]OIDV (0.46 ± 0.07%ID/g) in the cortex. Inhibition of OIDV binding showed that (-)-[125I]OIDV was selectively accumulated in regions known to express VAChT in the rat brain, and ex vivo autoradiography further confirmed these results showing similar accumulation of (-)-[125I]OIDV in these regions. Furthermore, (-)-[123I]OIDV for SPECT showed the same regional brain distribution as (-)-[125I]OIDV.
  
  
  CONCLUSIONS
  These results suggest that radioiodinated (-)-OIDV may be a potentially useful tool for studying presynaptic cholinergic neurons in the brain.
authors.affiliation: Division of Tracer Kinetics, Advanced Science Research Center, Kanazawa University, Ishikawa, 920-8640, Japan.|Clinical Laboratory, Kanazawa University Hospital, Kanazawa, Ishikawa, 920-8640, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Uno
authors.affiliation: Division of Tracer Kinetics, Advanced Science Research Center, Kanazawa University, Ishikawa, 920-8640, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kozaka
authors.affiliation: Division of Tracer Kinetics, Advanced Science Research Center, Kanazawa University, Ishikawa, 920-8640, Japan.|Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, 920-8640, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Miwa
authors.affiliation: Division of Tracer Kinetics, Advanced Science Research Center, Kanazawa University, Ishikawa, 920-8640, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Kitamura
authors.affiliation: National Institute of Nuclear Medicine and Allied Sciences; Bangladesh Atomic Energy Commission, BSM Medical University Campus, Dhaka-1000, Bangladesh.
authors.forename: Mohammad Anwar-Ul
authors.initials: MA
authors.lastname: Azim
authors.affiliation: Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, 920-8640, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ogawa
authors.affiliation: Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, 920-8640, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Taki
authors.affiliation: Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, 920-8640, Japan.
authors.forename: Seigo
authors.initials: S
authors.lastname: Kinuya
authors.affiliation: Division of Tracer Kinetics, Advanced Science Research Center, Kanazawa University, Ishikawa, 920-8640, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shiba
mesh_terms: D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D018360:Crystallography, X-Ray; D054879:Halogenation; D007536:Isomerism; D008024:Ligands; D008297:Male; D055620:Optical Phenomena; D010880:Piperidines / Q000737:chemistry* / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000378:metabolism; D014018:Tissue Distribution; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism*
chemical_list: D008024:Ligands; D010880:Piperidines; D019275:Radiopharmaceuticals; D017480:Receptors, sigma; D050494:Vesicular Acetylcholine Transport Proteins; C578221:o-iodo-trans-decalinvesamicol