An extended simplified reference tissue model for the quantification of dynamic PET with amphetamine challenge

Background: Equilibrium analysis to quantify dynamic positron emission tomography (PET) with bolus followed by continuous tracer infusion and acute amphetamine challenge assumes that all tissue kinetics attain steady states during pre- and post-challenge phases. Violations of this assumption may result in unreliable estimation of the amphetamine-induced percent change in the binding potential (Delta BP%). Method. We derived an extended simplified reference tissue model (ESRTM) for modeling tracer kinetics in the pre- and post-challenge phases. Ninety-minute [C-11]raclopride PET studies with bolus injection followed by continuous tracer infusion were performed on 18 monkeys and 2 baboons. Forty minutes after the bolus injection, a single acute intravenous amphetamine administration was given of 2.0 mg/kg to monkeys and of 0.05, 0.1, 0.5, and 1.5 mg/kg to baboons. Computer simulations further evaluated and characterized the ESRTM. Results: In monkey studies, the Delta BP% estimated by the ESRTM was 32 11, whereas, the Delta BP% obtained using the equilibrium methods was 32% to 81% lower. In baboon studies, the Delta BP% values estimated with the ESRTM showed a linear relationship between the Delta BP% and the natural logarithm of amphetamine dose (R-2=0.96), where the Delta BP % = 10.67Ln (dose)+ 33.79 (0.05 <= dose in mg/kg <= 1.5). At 1.5 mg/kg amphetamine, the Delta BP% estimates from equilibrium methods were 18% to 40% lower than those estimated by the ESRTM. Results showed that the nonsteady state of tracer kinetics produced an underestimation of the Delta BP% from the equilibrium analysis. The accuracy of the Delta BP% estimates from the equilibrium analysis was significantly improved by the ESRTM. The Delta BP% estimated by the ESRTM in the study was consistent with that from previous [C-11] raclopride PET with amphetamine challenge. Conclusion: In conclusion, the ESRTM is a robust kinetic modeling approach and is proposed for the quantification of dynamic PET with acute amphetamine stimulation. (c) 2006 Elsevier Inc. All rights reserved.