title: An extended simplified reference tissue model for the quantification of dynamic PET with amphetamine challenge.
abstract: 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 (DeltaBP%).
  
  
  METHODS
  We derived an extended simplified reference tissue model (ESRTM) for modeling tracer kinetics in the pre- and post-challenge phases. Ninety-minute [11C]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 DeltaBP% estimated by the ESRTM was 32+/-11, whereas, the DeltaBP% obtained using the equilibrium methods was 32% to 81% lower. In baboon studies, the DeltaBP% values estimated with the ESRTM showed a linear relationship between the DeltaBP% and the natural logarithm of amphetamine dose (R2=0.96), where the DeltaBP%=10.67Ln(dose)+33.79 (0.05<or=dose in mg/kg<or=1.5). At 1.5 mg/kg amphetamine, the DeltaBP% 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 DeltaBP% from the equilibrium analysis. The accuracy of the DeltaBP% estimates from the equilibrium analysis was significantly improved by the ESRTM. The DeltaBP% estimated by the ESRTM in the study was consistent with that from previous [11C] raclopride PET with amphetamine challenge.
  
  
  CONCLUSIONS
  In conclusion, the ESRTM is a robust kinetic modeling approach and is proposed for the quantification of dynamic PET with acute amphetamine stimulation.
authors.affiliation: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 601 N. Caroline St., JHOC room 3245, Baltimore, MD 21287, USA. yunzhou@jhmi.edu
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
authors.forename: Ming-Kai
authors.initials: MK
authors.lastname: Chen
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Endres
authors.forename: Weiguo
authors.initials: W
authors.lastname: Ye
authors.forename: James R
authors.initials: JR
authors.lastname: Brasić
authors.forename: Mohab
authors.initials: M
authors.lastname: Alexander
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Crabb
authors.forename: Tomás R
authors.initials: TR
authors.lastname: Guilarte
authors.forename: Dean F
authors.initials: DF
authors.lastname: Wong
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D001921:Brain / Q000033:anatomy & histology / Q000000981:diagnostic imaging*; D001931:Brain Mapping / Q000379:methods*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics*; D002531:Cerebellum / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000187:drug effects; D003198:Computer Simulation; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000000981:diagnostic imaging; D006801:Humans; D007700:Kinetics; D008959:Models, Neurological; D049268:Positron-Emission Tomography / Q000379:methods*; D020891:Raclopride / Q000493:pharmacokinetics*; D012016:Reference Values
chemical_list: D002250:Carbon Radioisotopes; D020891:Raclopride; D000661:Amphetamine