Distribution of tracer levels of cocaine in the human brain as assessed with averaged [11C]cocaine images.
The Ability of cocaine to block the dopamine transporter (DAT) in the nucleus accumbens, as well as its non-striatal and non-DAT actions, appears to be crucial for its reinforcing/rewardig effects. However, we have been unable to use PET and [11C]cocaine to map small regions with greater sensitivity due in part to the low specific to non-specific binding ration of [11C]cocaine. In order to increase the signal to noise ratio of the individual [11]cocaine images, we averaged the distribution volume (DV) PET images of 17 normal controls. In addition we also obtained averaged images for the dynamic set (14 time frames) and for the K1 values. The dynamic images were used to generate the average time activity curves from which we obtained the time required to half maximum clearance (T50). Twenty-nine ROIs were identified in the Talarach-Tournoux atlas and were then projected to the corregistered average PET image. The brain regions clustered in 3 groups according to their DV values. The highest activity (Group DV.1, 4.6-3.7) included putamen > accumbens > caudate. Intermediate DVs (Group DV.2, 3.2-2.8) included thalamus (mediodorsal and ventrolateral nucleus) > precuneus and posterior cingulate gyrus > amygdala, hippocampus, and temporal pole. Group DV.3 with low DVs (2.6-2.1) included the orbital cortex, precentral gyrus, and cerebellum. The brain regions clustered in 3 groups according to their T50 values. Regions with the faster clearance rates (15-20 minutes) included the orbital cortex, posterior cingulate, dorsomedial thalamus, precuneus, and cerebellum. Intermediate clearance rates (20-25 minutes) included caudate, putamen and accumbens regions with the slowest clearance rates (25-30 minuters) included caudate, putamen, and accumbens. In addition to the previously documented high binding of cocaine in striatum and moderate binding in thalamus in the living human brain this study also documents binding of cocaine in limbic and paralimbic brain regions. Further work is required to characterize the binding properties of cocaine in these brain areas and to elucidate their role in the reinforcing and addictive properties of cocaine.
Telang
F W
FW
Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA. ftelang@bnl.gov
Volkow
N D
ND
Levy
A
A
Logan
J
J
Fowler
J S
JS
Felder
C
C
Wong
C
C
Wang
G J
GJ
D000328:Adult; D001921:Brain / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000378:metabolism*; D003042:Cocaine / Q000493:pharmacokinetics*; D018765:Dopamine Uptake Inhibitors / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D014055:Tomography, Emission-Computed
D018765:Dopamine Uptake Inhibitors; D003042:Cocaine