- 作者：Kelly P. Cosgrove ; Julie K. Staley ; Ronald M. Baldwin ; Frederic Bois ; Christophe Plisson ; Mohammed S. Al-Tikriti ; John P. Seibyl ; Mark M. Goodman ; Gilles D. Tamagnan
- 关键词：SPECT ; Brain imaging ; Serotonin transporter ; Nonhuman primate ; [123I]p ZIENT
- 刊名：Nuclear Medicine and Biology
- 出版年：2010
- 出版时间：July 2010
- 年：2010
- 卷：37
- 期：5
- 页码：587-591
- 全文大小：222 K
IntroductionSerotonin dysfunction has been linked to a variety of psychiatric diseases; however, an adequate SPECT radioligand to probe the serotonin transporter system has not been successfully developed. The purpose of this study was to characterize and determine the in vivo selectivity of iodine-123-labeled 2β-carbomethoxy-3β-(4′-((Z)-2-iodoethenyl)phenyl)nortropane, [123I]p ZIENT, in nonhuman primate brain.Methods
Two ovariohysterectomized female baboons participated in nine studies (one bolus and eight bolus to constant infusion at a ratio of 9.0 h) to evaluate [123I]p ZIENT. To evaluate the selectivity of [123I]p ZIENT, the serotonin transporter blockers fenfluramine (1.5, 2.5 mg/kg) and citalopram (5 mg/kg), the dopamine transporter blocker methylphenidate (0.5 mg/kg) and the norepinephrine transporter blocker nisoxetine (1 mg/kg) were given at 8 h post-radiotracer injection.
Results
In the bolus to constant infusion studies, equilibrium was established by 4–8 h. [123I]p ZIENT was 93 % and 90 % protein bound in the two baboons and there was no detection of lipophilic radiolabeled metabolites entering the brain. In the high-density serotonin transporter regions (diencephalon and brainstem), fenfluramine and citalopram resulted in 35–71 % and 129–151 % displacement, respectively, whereas methylphenidate and nisoxetine did not produce significant changes (<10 % ).
Conclusion
These findings suggest that [123I]p ZIENT is a favorable compound for in vivo SPECT imaging of serotonin transporters with negligible binding to norepinephrine and dopamine transporters.