RT Journal Article SR Electronic T1 Imaging drug-induced dopamine release in rhesus monkeys with [11C]PHNO PET JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1773 OP 1773 VO 51 IS supplement 2 A1 Jean-Dominique Gallezot A1 David Weinzimmer A1 Krista Fowles A1 David Labaree A1 Ming-Qiang Zheng A1 Keunpoong Lim A1 Richard Carson A1 Evan Morris A1 Kelly Cosgrove YR 2010 UL http://jnm.snmjournals.org/content/51/supplement_2/1773.abstract AB 1773 Objectives The radiotracer [11C]PHNO has advantages over other dopamine D2 receptor ligands because it is an agonist and measures the high affinity, functionally active D2 receptors and not the low affinity D2 receptors. Ginovart et al. (2006) demonstrated improved sensitivity over [11C]raclopride for measuring amphetamine-induced changes in synaptic dopamine levels. Marenco et al. (2004) reported that a nicotine challenge (0.01-0.06 mg/kg, IV) resulted in a 5% reduction and an amphetamine challenge (0.4 mg/kg, IV) in a 28% reduction in [11C]raclopride binding potential in the caudate and putamen in monkey. The goal of this study was to investigate the sensitivity of [11C]PHNO to detect nicotine- and amphetamine-induced dopamine release in nonhuman primates. Methods Two adult male rhesus monkeys were imaged on a FOCUS 220 PET scanner after injection of a bolus of [11C]PHNO (mass dose <0.1 ug/kg) in 3 conditions: baseline; pre-injection of nicotine (0.1 mg/kg bolus + 0.07 mg/kg infusion over 30 min); amphetamine (0.4 mg/kg, 5 min prior to radiotracer injection). Four other animals participated in test-retest studies with bolus injections of [11C]PHNO on two separate days with the mass dose of PHNO kept constant at 0.1 ug/kg. The change in binding potential was assessed by SRTM2. Results Average test-retest variability in caudate and putamen was 6%. Nicotine administration resulted in an average decrease of 7.5 +7.0% in BPND in the caudate and putamen, with greater variability in the caudate. Amphetamine administration resulted in a robust 50.5+3.3% decrease in BPND in both the caudate and putamen. Conclusions Based on comparisons to literature values for [11C]raclopride these preliminary results are consistent with improved sensitivity of [11C]PHNO over [11C]raclopride for measuring amphetamine-induced dopamine release. Additionally, there may be greater sensitivity to detect small changes in dopamine release, such as from nicotine. Research Support NIDA (R03DA025820; KO1DA020651