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Sequential H₂¹⁵O PET Studies in Baboons: Before and After Amphetamine

¹ Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
² Mood and Anxiety Disorders Program, National Institutes of Mental Health, Bethesda, Maryland
³ Department of Biostatistics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

PET and ¹¹C-raclopride have been used to assess dopamine activity in vivo using a paradigm that involved d-amphetamine (AMPH)-induced endogenous dopamine release that led to reductions (relative to baseline) in the ¹¹C-raclopride-specific binding parameter (binding potential). A common assumption in bolus injection PET studies of this type is that cerebral blood flow (CBF) does not vary during the scan. The goal of this work was to examine the effect of AMPH administration on sequential PET measures of CBF. Methods: Eight dynamic H₂¹⁵O PET scans were acquired with arterial blood sampling in 6 baboons: 4 scans before AMPH (over 60 min) and 4 scans after AMPH (over 60 min) (0.6 mg/kg AMPH). Magnetic resonance images (coregistered to PET) were used to define regions of interest that included cortex, striatum (including subregions), and cerebellum. Data were analyzed using a 1-tissue compartment model. CBF was assessed through K₁ (mL/mL/min). Results: Temporal patterns of the CBF alterations were similar across regions for each baboon. For 5 of 6 baboons, a general pattern of an initial increase in K₁ was observed after AMPH that gradually declined toward baseline, after minimizing anesthesia-induced variability in the in vivo measures. Although these alterations after AMPH were statistically significant in particular subcortical regions and cerebellum, such changes would not likely influence measures of ¹¹C-raclopride binding potential to a significant extent. Conclusion: These data support previous PET studies for which constant blood flow was assumed during the bolus PET ¹¹C-raclopride/AMPH experiment across striatal subregions, while underscoring the importance of considering effects of anesthesia when interpreting in vivo imaging parameters.

Key Words: PET • blood flow • amphetamine

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