In vivo evaluation of [123I]mZIENT as a SPECT radioligand for the serotonin transporter

Introduction: In vivo imaging of the serotonin transporter continues to be a valuable tool in drug development and in monitoring diseases that alter serotonergic function. The purposes of this study were to: 1) evaluate the test/retest reproducibility of [123I] 2β-Carbomethoxy-3β-(3′-((Z)-2-iodoethenyl)phenyl)nortropane ([123I]mZIENT); and 2) to assess displacement of [123I]mZIENT following administration of SERT specific drugs. Methods: Six female baboons (Papio anubis) were scanned following i.v. administration of [123I]mZIENT. The regional binding potential (BPnd) was determined using a simplified reference tissue model, with the cerebellum used as a reference region. The test/retest reproducibility of BPnd was determined following repeated injection of [123I]mZIENT on a different day. To assess the displacement of [123I]mZIENT from SERT, citalopram (0.01–5 mg/kg) or sertraline (0.01–0.5 mg/kg) was given as iv bolus at ∼ 4 h following administration of [123I]mZIENT. Results: The test/retest variability of BPnd was less than 10% for all SERT-rich brain regions. Estimates of ED50 for displacement of [123I]mZIENT in SERT-rich regions were consistent with previous reports for the [11C] analog of [123I]mZIENT. Both citalopram and sertraline displaced [123I]mZIENT from SERT in a dose-dependent manner, with maximal observed displacements of greater than 80% in the diencephalon and greater than 75% in brainstem for both citalopram and sertraline. Conclusions: [123I] mZIENT demonstrates good test–retest reproducibility; and initial displacement studies suggest that this compound is highly selective for SERT. Overall, this radioligand has favorable characteristics for use in drug development studies and/or longitudinal studies interrogating SERT.