Abstract
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Objectives: Sigma-1 receptor plays an important role of remission of the stress. We synthesized vesamicol analogs with various ring size and investigated the affinity of those vesamicol analogs to sigma-1 receptor. As a results, vesamicol analog with 5-membered ring structure (OI5V) showed high selective binding affinity for sigma-1 receptor. In this study, we performed in vivo evaluation of [125I]OI5V as a potential sigma-1 receptor imaging probe.
Methods: [125I]OI5V was prepared from o-tributylstannyl-cyclopentanevesamicol(OT5V) by iododestannylation reaction under no-carrier-added conditions. [125I]OI5V was injected I/V into mice. The mice were sacrificed at 10, 30, 60 and 120 min postinjection and interest organs were collected, weighed and counted to investigate the biodistribution. In vivo blocking study were performed to reveal the binding selectivity of [125I]OI5V to sigma-1 receptor in vivo.
Results: [125I]OI5V was obtained with radiochemical purity of greater than 99%, and the radiochemical yield was 79%. Partition coefficient(log P) of [125I]OI5V was 2.22 ± 0.07. Biodistribution study showed high uptake (about 13.9 %ID/g) of [125I]OI5V in brain at 30 min postinjection. The uptake of [125I]OI5V in brain was significantly blocked by coadministration of 375 nmol pentazocine and 375 nmol haloperidol.
Conclusion: These results showed that [125I]OI5V bound selectively to sigma-1 receptor in rat brain in vivo. Radioiodinated OI5V labeled with 123I was suggested to be useful as a sigma-1 receptor imaging agent for SPECT. Biodistribution of [125I]OI5V in mice 30 min post-injection. Time course of brain uptake ( %dose/g) of [125I]OI5V in mice.