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 [I-123] 2 beta-Carbomethoxy-3 beta-(3'-((Z)-2-iodoethenyl)phenyl)nortropane ([I-123]mZIENT); and 2) to assess displacement of [(123)]mZIENT following administration of SERT specific drugs. Methods: Six female baboons (Papio anubis) were scanned following iv. administration of [(123)]mZIENT. The regional binding potential (BP) 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 [I-123]mZIENT on a different day. To assess the displacement of [I-123]mZIENT from SERT, citalopram (0.01-5 mg/kg) or sertraline (0.01-0.5 mg/kg) was given as iv bolus at similar to 4h following administration of [I-123]mZIENT. Results: The test/retest variability of BPnd was less than 10% for all SERT-rich brain regions. Estimates of ED50 for displacement of [I-123]mZIENT in SERT-rich regions were consistent with previous reports for the (C-11] analog of [I-123]mZIENT. Both citalopram and sertraline displaced [I-123]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: [I-123]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. (C) 2012 Elsevier Inc. All rights reserved.