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

Abstract Introduction 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 2β-carbomethoxy-3β-(4′-(( Z )-2-iodoethenyl)phenyl)nortropane, [123 I] 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 [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. Results 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 (