Abstract
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Objectives: To non-invasively measure the latent period in the amphetamine-induced displacement of [11C]raclopride. Methods: Twenty six cynomologous monkeys and six Papio anubis baboons were studied. [11C]raclopride (~25 mCi) at high specific activity administrated by bolus plus continuous infusion at Kbol = 75 min, i.e., bolus dose is 46% of the total dose. The 90-min dynamic PET scan of 30 frames (4x0.25, 4x0.5, 3x1,2x2,5x4,12x5 min) was performed on a GE Advance scanner and started at the beginning of tracer injection. Forty minutes after tracer injection, amphetamine (2.0 mg/kg) was injected intravenously over 2 minutes. A parameter (dt) that represents a latent period in the amphetamine-induced displacement of tracer with the ESRTM (R1, k2, BP0, BP1) (Zhou et al., Neuroimage 2006, 33(2):550-63) called ESRTMdt was proposed for modeling tracer kinetics in the baseline phase [0 40+dt] and the displacement phase [40+dt 90]. A nonlinear regression method using the Marquardt algorithm was used to estimate R1, k2, BP0, BP1, and dt by fitting the ESRTMdt to the measured striatum time radioactivity curve. Results: The ESRTMdt provided the best model fitting as compared to the ESRTM with the given dt values suggested by previous published microdialysis studies. The latent period dt estimated by the ESRTMdt was 12.4 ± 3.7 (n = 26) and 5.8 ± 3.3 (n = 7) (mean ± SD) minutes for monkeys and baboons, respectively. The amphetamine-induced percent change in the tracer binding potential (BP) from baseline BP0 obtained by ESRTMdt fitting was (27 ± 9)% and (34 ± 9)% for monkeys and baboons, respectively. Conclusions: We first propose a non-invasive in vivo approach to estimate the latent period in the amphetamine-induced displacement of [11C]raclopride in striatum. The estimated latent period values from the study will be useful for optimization of experimental design in dynamic PET study with amphetamine challenge and for improvements on the accuracy of estimates. The approach is applicable to other tracer studies with amphetamine stimulations.
Research Support (if any): Grant support AA12839, DA00412, NS38927
- Society of Nuclear Medicine, Inc.