Experimental Design After overnight abstinence, each subject was scanned on separate days in the a.m. verified by exhaled expired-air carbon monoxide (CO) < 10 ppm. The subjects were given [11C]raclopride in a counterbalanced (days) design. Unknown to the smokers, two denic tobacco cigarettes were always smoked first. Two nic cigarettes were 17-AAG solubility smoked about two hr later. The reason two cigarettes were smoked was because of the unusually inefficient method of smoking with a cigarette inside a bottle. Each subject arrived at the PET unit about 7:30 a.m. on two separate days about a week apart. After proper positioning and controls, the radiotracer was given about 8:30 a.m. The first set of scans were with [11C]raclopride and denic tobacco smoking. The second set of scans with [11C]raclopride were with nic tobacco smoking.

The experimental timeline is illustrated in Figure 1 with venous plasma nicotine concentrations before and after smoking each type of tobacco cigarette. Figure 1. Radioligand dose, tobacco smoking, venous plasma nicotine time line. The first radioligand [11C] dose was given about 8:30 a.m. After its radioactivity decayed, the second dose [11C] was given about 10:30 a.m. Smoking denic tobacco cigarettes produced … Neuroimaging and Image Data Analysis The detailed imaging methods and data analysis were similar to those described in Scott et al. (2007). PET scans were acquired with a Siemens HR+ scanner in three-dimensional (3D) mode (reconstructed full width at half maximum resolution ~5.5 mm in-plane and 5.0 mm axially) with septa retracted and scatter correction.

Participants were positioned in the PET scanner gantry and two intravenous (i.v.) (antecubital) lines placed. A light forehead restraint was used to eliminate intrascan movement. [11C]Raclopride was synthesized at high specific activity (>2000 Ci/mmol) by the reaction of O-desmethyl raclopride with [11C]methyl triflate. In each of the two scans, 10�C15 mCi was administered. The total mass of raclopride was 0.089 �� 0.047 ��g/kg per scan. Fifty percent of the radiotracer dose was administered as a bolus and the remaining 50% by continuous infusion for the rest of the study. Images were reconstructed using iterative algorithms (brain mode: FORE/OSEM four iterations; 17 subjects; no smoothing) into a 128 �� 128 pixel matrix in a 28.8 cm diameter field of view. Attenuation corrections Cilengitide were performed through a 6-min transmission scan (68Ge source) obtained before the PET study, also with iterative reconstruction of the blank/transmission data followed by segmentation of the attenuation image. Small head motions were corrected by an automatic computer algorithm for each subject and the images coregistered (Minoshima et al., 1993).