In vivo evaluation of [¹²³I]mZIENT as a SPECT radioligand for the serotonin transporter.
BACKGROUND
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 (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.
Institute for Neurodegenerative Disorders, New Haven, CT 06510, USA. jrbatis6@gmail.com
Jeffery
J
Batis
Olivier
O
Barret
David
D
Alagille
Andrei O
AO
Koren
Jeffrey S
JS
Stehouwer
Kelly
K
Cosgrove
Mark
M
Goodman
John
J
Seibyl
Gilles
G
Tamagnan
D000818:Animals; D001667:Binding, Competitive; D015283:Citalopram / Q000378:metabolism; D005260:Female; D007457:Iodine Radioisotopes; D008024:Ligands; D009662:Nortropanes / Q000378:metabolism* / Q000493:pharmacokinetics; D010215:Papio; D015203:Reproducibility of Results; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D020280:Sertraline / Q000378:metabolism; D013379:Substrate Specificity; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
C516221:2-carbomethoxy-3-(3'-(2-iodoethenyl)phenyl)nortropane; D007457:Iodine Radioisotopes; D008024:Ligands; D009662:Nortropanes; D050486:Serotonin Plasma Membrane Transport Proteins; D015283:Citalopram; D020280:Sertraline