A radiotracer method to study efflux transport of iodide liberated from thyroid hormones via deiodination metabolism in the brain

AimsThyroid 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.Main methods6-[125I]Iodo-9-pentylpurine ([125I]9Pe6IP) was designed to enter the brain and release 125I− by the reaction with glutathione and synthesized from the corresponding bromo derivative in a Br/125I exchange reaction. The brain kinetics of radioactivity and radioactive metabolites were investigated after intravenous injection of [125I]9Pe6IP into mice. The iodide efflux rate was estimated in mice pretreated with perchlorate, an inhibitor of iodide transport from the brain.Key findingsHigh brain uptake (5.3% injected dose/g) was observed at 1 min, and almost complete conversion of [125I]9Pe6IP to 125I− occurred 10 min after injection. The 125I− uptake from the blood was negligible. 125I− was eliminated from the brain along a single-exponential curve with a half-life of 6.0 min. Furthermore, dose-dependent inhibition of 125I− efflux was observed in mice pretreated with perchlorate.SignificanceWe conclude that 9Pe6IP labeled with 124I (positron emitter) or 123I (single-photon emitter) may be useful for studying the in vivo efflux transport of iodide in the brain using nuclear medicine imaging devices.