In vivo evaluation of [¹²³I]mZIENT as a SPECT radioligand for the serotonin transporter.
Nucl Med Biol
; 39(8): 1137-41, 2012 Nov.
Article
em En
| MEDLINE
| ID: mdl-23084043
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 [¹²³I] 2ß-Carbomethoxy-3ß-(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 (BP(nd)) was determined using a simplified reference tissue model, with the cerebellum used as a reference region. The test/retest reproducibility of BP(nd) was determined following repeated injection of [¹²³I]mZIENT on a different day. To assess the displacement of [¹²³I]mZIENT from SERT, citalopram (0.01-5mg/kg) or sertraline (0.01-0.5mg/kg) was given as iv bolus at ~4h following administration of [¹²³I]mZIENT.RESULTS:
The test/retest variability of BP(nd) 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tomografia Computadorizada de Emissão de Fóton Único
/
Proteínas da Membrana Plasmática de Transporte de Serotonina
/
Nortropanos
Tipo de estudo:
Observational_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Nucl Med Biol
Assunto da revista:
BIOLOGIA
/
MEDICINA NUCLEAR
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos