SPECT imaging with the serotonin transporter radiotracer [123I]p ZIENT in nonhuman primate brain.
BACKGROUND
Serotonin dysfunction has been linked to a variety of psychiatric diseases; however, an adequate SPECT radioligand to probe the serotonin transporter system has not been successfully developed. The purpose of this study was to characterize and determine the in vivo selectivity of iodine-123-labeled 2beta-carbomethoxy-3beta-(4'-((Z)-2-iodoethenyl)phenyl)nortropane, [(123)I]p ZIENT, in nonhuman primate brain.


METHODS
Two ovariohysterectomized female baboons participated in nine studies (one bolus and eight bolus to constant infusion at a ratio of 9.0 h) to evaluate [(123)I]p ZIENT. To evaluate the selectivity of [(123)I]p ZIENT, the serotonin transporter blockers fenfluramine (1.5, 2.5 mg/kg) and citalopram (5 mg/kg), the dopamine transporter blocker methylphenidate (0.5 mg/kg) and the norepinephrine transporter blocker nisoxetine (1 mg/kg) were given at 8 h post-radiotracer injection.


RESULTS
In the bolus to constant infusion studies, equilibrium was established by 4-8 h. [(123)I]p ZIENT was 93% and 90% protein bound in the two baboons and there was no detection of lipophilic radiolabeled metabolites entering the brain. In the high-density serotonin transporter regions (diencephalon and brainstem), fenfluramine and citalopram resulted in 35-71% and 129-151% displacement, respectively, whereas methylphenidate and nisoxetine did not produce significant changes (<10%).


CONCLUSIONS
These findings suggest that [(123)I]p ZIENT is a favorable compound for in vivo SPECT imaging of serotonin transporters with negligible binding to norepinephrine and dopamine transporters.
Cosgrove
Kelly P
KP
Yale University School of Medicine, VA Connecticut HCS (116A6), West Haven, CT 06516, USA. kelly.cosgrove@yale.edu
Staley
Julie K
JK
Baldwin
Ronald M
RM
Bois
Frederic
F
Plisson
Christophe
C
Al-Tikriti
Mohammed S
MS
Seibyl
John P
JP
Goodman
Mark M
MM
Tamagnan
Gilles D
GD
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D007457:Iodine Radioisotopes; D009662:Nortropanes / Q000378:metabolism* / Q000493:pharmacokinetics; D010215:Papio; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013379:Substrate Specificity; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
C472792:2-carbomethoxy-3-(4'-(2-iodoethenyl)phenyl)nortropane; D007457:Iodine Radioisotopes; D009662:Nortropanes; D050486:Serotonin Plasma Membrane Transport Proteins