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 nucle us accumbens, as well as its non-striatal and non-DAT actions, appears to b e crucial for its reinforcing/rewardig effects. However, we have been unabl e 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]coc aine. 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 n ormal controls. In addition we also obtained averaged images for the dynami c 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 tim e required to half maximum clearance (T-50) Twenty-nine ROIs were identifie d in the Talarach-Tournoux atlas and were then projected to the corregister ed 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 putame n > accumbens > caudate. Intermediate DVs (Group DV.2, 3.2-2.8) included th alamus (mediodorsal and ventrolateral nucleus) > precuneus and posterior ci ngulate gyrus. amygdala, hippocampus, and temporal pole. Group DV.3 with lo w DVs (2.6-2.1) included the orbital cortex, precentral gyrus, and cerebell um. The brain regions clustered in 3 groups according to their T-50 values. Regions with the faster clearance rates (15-20 minutes) included the orbit al cortex, posterior cingulate, dorsomedial thalamus, precuneus, and cerebe llum. Intermediate clearance rates (20-25 minutes) included caudate, putame n and accumbens regions with the slowest clearance rates (25-30 minuters) i ncluded caudate, putamen, and accumbens. In addition to the previously docu mented 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 characteri ze the binding properties of cocaine in these brain areas and to elucidate their role in the reinforcing and addictive properties of cocaine. Synapse 31:290-296, 1999. (C) 1999 Wiley-Liss, Inc.