[11C]beta-CIT-FE, a radioligand for quantitation of the dopamine transporter in the living brain using positron emission tomography.
The cocaine analogue beta-CIT-FE (N-(2-fluoroethyl)-2 beta-carbomethoxy-3 beta-(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]beta-CIT-FE accumulated in the striatum with a striatum-to-cerebellum ratio of about 9 after 60 min. Pseudoequilibrium of specific [11C]beta-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 beta-CIT or the dopamine transporter inhibitor GBR 12909, indicating that striatal radioactivity following injection of [11C]beta-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]beta-CIT-FE has potential as a useful PET radioligand for quantitation of the dopamine transporter in the primate brain in vivo.
Halldin
C
C
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
Farde
L
L
Lundkvist
C
C
Ginovart
N
N
Nakashima
Y
Y
Karlsson
P
P
Swahn
C G
CG
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D003042:Cocaine / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins; D008252:Macaca fascicularis; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009662:Nortropanes / Q000378:metabolism*; D011869:Radioligand Assay; D013997:Time Factors; D014055:Tomography, Emission-Computed
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; C097058:N-(2-fluoroethyl)-2-carbomethoxy-3-(4-iodophenyl)nortropane; D009419:Nerve Tissue Proteins; D009662:Nortropanes; D003042:Cocaine