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  • Title: Characterization of the dopamine transporter in nonhuman primate brain: homogenate binding, whole body imaging, and ex vivo autoradiography using [125I] and [123I]IPCIT.
    Author: al-Tikriti MS, Zea-Ponce Y, Baldwin RM, Zoghbi SS, Laruelle M, Seibyl JP, Giddings SS, Scanley BE, Charney DS, Hoffer PB.
    Journal: Nucl Med Biol; 1995 Jul; 22(5):649-58. PubMed ID: 7581176.
    Abstract:
    IPCIT [2 beta-carboisopropoxy-3 beta-(4-iodophenyl)tropane; also designated RTI-121] is the isopropyl ester of beta-CIT [2 beta-carbomethoxy-3 beta-(4-iodophenyl) tropane]. Although beta-CIT binds to dopamine (DA), serotonin (5-HT) and norepinephrine (NE) transporters, IPCIT has been reported to be selective for the DA transporter. IPCIT was labeled with 125I and its receptor binding to membranes prepared from baboon striatum was compared with that of [125I] beta-CIT. These studies confirmed the relative selectivity of IPCIT for the DA transporter in comparison to 5-HT and NE transporters. The nonspecific binding of [125I]IPCIT was almost four times greater than that of [125I] beta-CIT. The biodistribution of IPCIT was examined in two baboons with whole body imaging for 24-30 h after administration of 3 mCi of 123I-labeled tracer. The brain uptake peaked within the first hour at 9.2% of the injected dose and the majority of activity in the body cleared through the hepatobiliary system. The distribution of activity within the brain was examined with ex vivo autoradiography in one monkey injected with [123I]IPCIT. Activity was concentrated in the caudate and putamen and had values of 5 and 7 microCi/cm3 per microCi/g, respectively. The distribution in brain regions receiving moderately dense serotonergic innervation (e.g. superior colliculus and thalamus) had levels of activity equivalent to that in cerebellum. This study confirmed the in vitro and in vivo selectivity of IPCIT for the DA transporter but also showed that [125I]IPCIT had higher in vitro nonspecific binding than [125I] beta-CIT.
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