The objective of the study is to improve the quantification of [11C]raclopride dynamic PET with amphetamine challenges. Methods: [11C]raclopride was performed on two groups: (1) 19 Rhesus monkeys (3-5 kg) scanned on a HRRT scanner; (2) 26 cynomologous monkeys (5-9 kg) and 6 Papio anubis baboons (17-27 kg) scanned on a GE Advance scanner. [11C]raclopride (18-25 mCi) at high specific activity was administrated by bolus plus continuous infusion at Kbol = 75 min. Ninety-min dynamic PET scanning was started immediately after tracer injection. Forty min post tracer injection, amphetamine (2 mg/kg) was injected intravenously over 2 min. The dynamic images of 30 frames (4x0.25, 4x0.5, 3x1, 2x2, 5x4, 12x5) were reconstructed in each study. A parameter (dt) that represents a latent period in the amphetamine-induced displacement of tracer with an ESRTM (R1, k2, BP0, BP1) (Zhou et al., Neuroimage 2006, 33(2):550-63) called ESRTMdt (R1, k2, BP0, BP1, dt) was proposed for modeling tracer kinetics in the baseline phase [0 T0+dt] and the displacement phase [T0+dt T] as below: where T0 = 40 min, T = 90, and the CT(t) and CREF(t) represent the tracer concentrations at time t for target and reference tissues, respectively. R1 is the target to reference tissue ratio of transport rate constant, k2 is the efflux rate constant of target tissue, BP0 and BP1 are the tracer binding potentials in target tissue in baseline and displacement phases, respectively. A Marquardt algorithm was used to estimate parameters by fitting the ESRTMdt to the measured striatum time activity curve. For comparison, the ESRTM with given dt in [0 30] was also applied to the same data set. The amphetamine-induced percent decrease in BP ( BP%) (= 100(BP0-BP1)/BP0) were calculated. Results: Based on the Akaike information criterion, the ESRTMdt provided the best model fitting as compared to the ESRTM. The estimates of (R1, k2, BP0, BP% and dt) (mean ± SD) from ESRTMdt fitting were (0.86 ± 0.08, 0.13 ± 0.02, 2.85 ± 0.30, 28 ± 9 and 12.43 ± 3.73) for cynomologous monkeys, (0.96 ± 0.09, 0.18 ± 0.02, 4.88 ± 0.66, 28 ± 8, and 14.15 ± 6.17) for Rhesus monkeys, and (0.91 ± 0.04, 0.18 ± 0.02, 2.97 ± 0.32, 46 ± 5, and 6.66 ± 1.69) for baboons. The estimates of BP% from ESRTM fitting decreased monotonically in the given dt. Conclusions: The ESRTMdt provided better model fitting significantly as compared to the ESRTM with given dt. The estimates of BP% from ESRTM fitting were sensitive to the pre-assumed latent period (dt). The estimated latent period values from the study will be useful for the optimization of experimental design in PET study with amphetamine challenge. Grant support: AA12839, DA00412, NS38927, MH075378, ES07062, ES019075, and Michael J. Fox Foundation for Parkinson's Research.
|Original language||English (US)|
|Journal||Journal of Cerebral Blood Flow and Metabolism|
|Issue number||SUPPL. 1|
|State||Published - Nov 13 2007|
ASJC Scopus subject areas
- Clinical Neurology
- Cardiology and Cardiovascular Medicine