Study design.
Participants had two sets of PET [11C]raclopride scans (with placebo and with intravenous MP): one before treatment initiation (treatment-naive) and one after 12 months of clinical treatment with oral MP (long-term treatment). Clinical treatment with oral MP was provided during the intervening 12 months between scanning sessions. The mean total daily dose of MP was in the vicinity of 1 mg/kg or its equivalent in long-acting dose form [i.e., osmotic release oral system (OROS) MP]. Participants were titrated to a mean dose of 75 mg. The dose is above the maximum labeled dose of OROS MP, because titration was managed according to clinical best practice to maximize efficacy. Progress of treatment was followed using the clinical global impressions improvement and severity scales (Guy, 2000) at each medication visit. Subjects were titrated in open manner during weekly medication visits until they reached optimal response and the dose was stabilized. The PET scans for the long-term treatment condition were conducted 24–48 h after the last clinical dose of MP to allow for the levels of MP from the final dose to dissipate before the PET study (Modi et al., 2000). To corroborate this, we measured plasma MP levels before intravenous injection of MP to ensure that they were nondetectable.
Scans.
PET scans were obtained with a Siemens HR+ tomograph [resolution, 4.5 × 4.5 × 4.5 mm full-width half-maximum (FWHM)] in 3D mode. Each subject underwent two sets of paired scans with [11C]raclopride (total of four scans); for each set, one scan was done after intravenous placebo (3 cc saline) and one after intravenous MP (0.5 mg/kg). The study used a single blind design (subjects were blind to the drugs received). Dynamic scans were started immediately after injection of 4–8 mCi of [11C]raclopride (specific activity, 0.5–1.5 Ci/μM at end of bombardment). Dynamic scans were obtained for a total of 60 min as described previously (Volkow et al., 1994). Arterial blood was obtained throughout the procedure to measure the concentration of unchanged [11C]raclopride in plasma (Alexoff et al., 1995