[11C]?-CIT-FE, a radioligand for quantitation of the dopamine transporter in the living brain using positron emission tomography

Abstract

The cocaine analogue β‐CIT‐FE (N‐(2‐fluoroethyl)‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)nortropane) was labeled with 11C for positron emission tomography (PET) studies of the dopamine transporter. After intravenous administration to a cynomolgus monkey, [11C]β‐CIT‐FE accumulated in the striatum with a striatum‐to‐cerebellum ratio of about 9 after 60 min. Pseudoequilibrium of specific [11C]β‐CIT‐FE binding in the striatum was obtained within 30–50 min. The radioactivity ratios of the thalamus to the cerebellum and the neocortex to the cerebellum were about 2 and 1.5, respectively. In displacement and pretreatment experiments, radioactivity in the striatum but not in the cerebellum was reduced after injection of β‐CIT or the dopamine transporter inhibitor GBR 12909, indicating that striatal radioactivity following injection of [11C]β‐CIT‐FE represents reversible binding to dopamine transporter sites. After displacement or pretreatment with cocaine there was a marked effect not only in the striatum but also in the thalamus and neocortex. [11C]β‐CIT‐FE has potential as a useful PET radioligand for quantitation of the dopamine transporter in the primate brain in vivo. © 1996 Wiley‐Liss, Inc.

PE2I: A Radiopharmaceutical forIn vivoExploration of the Dopamine Transporter

“…Specific binding represented by the striatum and the substantia nigra to cerebellum ratios were 10 and 1.8, respectively, at peak equilibrium. These ratios were higher than those obtained for other DAT ligands such as [ 11 C]FE‐CIT (Farde et al 2000; Halldin et al 1996). The rapid peak equilibrium, added to the high specific binding not only in the striatum but also in the thalamic region, may be of advantage for subregional analysis of the striatum in neuropsychiatric disorders.…”

Synthesis and amine transporter affinities of novel phenyltropane derivatives as potential positron emission tomography (PET) imaging agents

“…Most PET radiotracers developed to target monoamine transporters have been radiocarbon [ 11 C]-labeled phenyltropanes. [20][21][22][23][24][25][26][27] There are a few available [ 18 F]-labeled tracers for amine transporters, but most of them require multi-step radiosynthesis. 28-37 Moreover, the selectivity of such compounds for specific monoamine transporters varies, and requires further improvement.…”

Regulation of dopaminergic activity in early Parkinson's disease

“…24 Several DAT ligands have been applied as single-photon emission computed tomography or PET tracers for the visualization of the dopaminergic system in PD. 19,[25][26][27] The DAT tracer [ 11 C]CIT-FE is a fluoroethyl analogue of the more commonly used [ 11 C]CIT, with kinetic properties more suitable for PET studies. 19 The magnitude of reduction reported for patients in early stages of PD varies considerably between different tracers and could be explained by several factors.…”

“…19,[25][26][27] The DAT tracer [ 11 C]CIT-FE is a fluoroethyl analogue of the more commonly used [ 11 C]CIT, with kinetic properties more suitable for PET studies. 19 The magnitude of reduction reported for patients in early stages of PD varies considerably between different tracers and could be explained by several factors. Patient selection, technical equipment, tracer selection, and anatomical positioning of the measured regions are obvious factors influencing the results.…”