SPECT imaging with the serotonin transporter radiotracer [¹²³I]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, [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.

Keywords: SPECT, Brain imaging, Serotonin transporter, Nonhuman primate, [¹²³I]p ZIENT