A radiotracer method to study efflux transport of iodide liberated from thyroid hormones via deiodination metabolism in the brain.
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.
Okamura
Toshimitsu
T
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.
Igarashi
Jun
J
Kikuchi
Tatsuya
T
Fukushi
Kiyoshi
K
Arano
Yasushi
Y
Irie
Toshiaki
T
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
D007457:Iodine Radioisotopes; D010472:Perchlorates; D027981:Symporters; D013963:Thyroid Hormones; D000099209:Sodium-Iodide Symporters; C494474:perchlorate