PET study of [11C]beta-CIT binding to monoamine transporters in the monkey and human brain.
The cocaine congener beta-CIT has been labeled with 11C for positron emission tomographic (PET) studies of the dopamine transporter. In the present autoradiographic study on human brain sections and PET study on monkey and human [11C]beta-CIT accumulated markedly in the striatum. [11C]beta-CIT binding in the striatum was selective to the dopamine transporter. The binding in the thalamus was on an intermediate level and was displaced by compounds having affinity for norepinephrine and serotonin transporters. The neocortical binding was on a low level and could be displaced only by citalopram, a serotonin uptake inhibitor. A high dose of cocaine intravenously (7 mg/kg) induced a 50% occupancy of specific [11C]beta-CIT binding to the dopamine transporter in the striatum. This dose is much higher than the doses of 0.25-0.5 mg/kg i.v. for cocaine arousal in human subjects. The finding indicates that cocaine arousal may be induced at a low dopamine transporter occupancy of a few percent. [11C]beta-CIT should be a useful radioligand to explore cocaine actions in humans and to follow the pathophysiological process in vivo by PET in neurodegenerative diseases of the striatum.
Farde
L
L
Department of Psychiatry and Psychology, Karolinska Hospital, Stockholm, Sweden.
Halldin
C
C
Müller
L
L
Suhara
T
T
Karlsson
P
P
Hall
H
H
D000328:Adult; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives* / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes; D008253:Macaca mulatta / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D050484:Norepinephrine Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D050492:Vesicular Biogenic Amine Transport Proteins
D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D006023:Glycoproteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters; D050492:Vesicular Biogenic Amine Transport Proteins; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine