SPECT imaging with the serotonin transporter radiotracer [123I]p ZIENT in nonhuman primate brain.

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

Yale University School of Medicine, VA Connecticut HCS (116A6), West Haven, CT 06516, USA. kelly.cosgrove@yale.edu

Nuclear medicine and biology 2010 Jul

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Serotonin 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 2beta-carbomethoxy-3beta-(4'-((Z)-2-iodoethenyl)phenyl)nortropane, [(123)I]p ZIENT, in nonhuman primate brain. 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 [(123)I]p ZIENT. To evaluate the selectivity of [(123)I]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. In the bolus to constant infusion studies, equilibrium was established by 4-8 h. [(123)I]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%). These findings suggest that [(123)I]p ZIENT is a favorable compound for in vivo SPECT imaging of serotonin transporters with negligible binding to norepinephrine and dopamine transporters. Copyright 2010 Elsevier Inc. All rights reserved.

Citation

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. SPECT imaging with the serotonin transporter radiotracer [123I]p ZIENT in nonhuman primate brain. Nuclear medicine and biology. 2010 Jul;37(5):587-91