title: A radiotracer method to study efflux transport of iodide liberated from thyroid hormones via deiodination metabolism in the brain.
abstract: OBJECTIVE
  Thyroid hormones (TH) play an important role in the development and functional maintenance of the central nervous system. The purpose of this study was to develop a radiotracer method for studying the in vivo efflux transport of iodide liberated by the TH metabolism in the brain. The rationale of our method is as follows: a radioiodinated compound can enter the brain and rapidly release iodide in situ; the iodide efflux rate can be estimated from the clearance of brain radioactivity after disappearance of the iodinated compound.
  
  
  METHODS
  6-[(125)I]Iodo-9-pentylpurine ([(125)I]9Pe6IP) was designed to enter the brain and release (125)I(-) by the reaction with glutathione and synthesized from the corresponding bromo derivative in a Br/(125)I exchange reaction. The brain kinetics of radioactivity and radioactive metabolites were investigated after intravenous injection of [(125)I]9Pe6IP into mice. The iodide efflux rate was estimated in mice pretreated with perchlorate, an inhibitor of iodide transport from the brain.
  
  
  RESULTS
  High brain uptake (5.3% injected dose/g) was observed at 1 min, and almost complete conversion of [(125)I]9Pe6IP to (125)I(-) occurred 10 min after injection. The (125)I(-) uptake from the blood was negligible. (125)I(-) was eliminated from the brain along a single-exponential curve with a half-life of 6.0 min. Furthermore, dose-dependent inhibition of (125)I(-) efflux was observed in mice pretreated with perchlorate.
  
  
  CONCLUSIONS
  We conclude that 9Pe6IP labeled with (124)I (positron emitter) or (123)I (single-photon emitter) may be useful for studying the in vivo efflux transport of iodide in the brain using nuclear medicine imaging devices.
authors.affiliation: Probe Research Section, Department of Molecular Probe, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba-shi, Chiba 263-8555, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Okamura
authors.forename: Jun
authors.initials: J
authors.lastname: Igarashi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Fukushi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Arano
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Irie
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004334:Drug Administration Schedule; D006801:Humans; D007457:Iodine Radioisotopes / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D051379:Mice; D010472:Perchlorates / Q000008:administration & dosage / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D027981:Symporters / Q000037:antagonists & inhibitors; D013963:Thyroid Hormones / Q000032:analysis / Q000378:metabolism*; D000099209:Sodium-Iodide Symporters
chemical_list: D007457:Iodine Radioisotopes; D010472:Perchlorates; D027981:Symporters; D013963:Thyroid Hormones; D000099209:Sodium-Iodide Symporters; C494474:perchlorate