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

• Published in: Nuclear medicine and biology 2012-11, Vol.39 (8), p.1137-1141
• Main Authors: Batis, Jeffery, Barret, Olivier, Alagille, David, Koren, Andrei O, Stehouwer, Jeffrey S, Cosgrove, Kelly, Goodman, Mark, Seibyl, John, Tamagnan, Gilles
• Format: Article
• Language: English
• Subjects: [123I]mZIENT; Animals; Binding, Competitive; Biological and medical sciences; Citalopram - metabolism; Contrast media. Radiopharmaceuticals; Female; Iodine Radioisotopes; Ligands; Medical sciences; Nonhuman primate; Nortropanes - metabolism; Nortropanes - pharmacokinetics; Papio; Pharmacology. Drug treatments; Radiology; Reproducibility of Results; Serotonin Plasma Membrane Transport Proteins - metabolism; SERT; Sertraline - metabolism; SPECT; Substrate Specificity; Tomography, Emission-Computed, Single-Photon - methods
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/j.nucmedbio.2012.07.006

Abstract 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 [123 I] 2β-Carbomethoxy-3β-(3′-((Z)-2-iodoethenyl)phenyl)nortropane ([123 I]mZIENT); and 2) to assess displacement of [123 I]mZIENT following administration of SERT specific drugs. Methods Six female baboons ( Papio anubis ) were scanned following i.v. administration of [123 I]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 [123 I]mZIENT on a different day. To assess the displacement of [123 I]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 [123 I]mZIENT. Results The test/retest variability of BPnd was less than 10% for all SERT-rich brain regions. Estimates of ED50 for displacement of [123 I]mZIENT in SERT-rich regions were consistent with previous reports for the [11 C] analog of [123 I]mZIENT. Both citalopram and sertraline displaced [123 I]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 [123 I] 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.