MicroPET/CT assessment of FDG uptake in brain after long-term methylphenidate treatment in nonhuman primates.
Methylphenidate (MPH) is a psychostimulant commonly used for the treatment of Attention-Deficit Hyperactivity Disorder (ADHD). Since the long-term effects of this drug on the central nervous system (CNS) are not well understood, we conducted microPET/CT scans on young adult male rhesus monkeys (n=4/group) to gather information on brain metabolism using the uptake of [(18)F]Fluoro-2-deoxy-2-d-glucose (FDG) as a marker. Approximately two-year old, male rhesus monkeys were treated orally with MPH twice per day, five days per week (M-F) over a 6-year period. Subjects received MPH at either 2.5 or 12.5mg/kg/dose or vehicle (Prang). To minimize the acute effects of MPH on FDG uptake, microPET/CT scans were scheduled on Mondays before their first daily dosing of the week (approximately 68h since their last treatment). FDG (370±8.88MBq) was injected intravenously and 30min later microPET/CT images were obtained over 60min. Radiolabeled tracer accumulation in regions of interest (ROIs) in the prefrontal cortex, temporal cortex, striatum and cerebellum were converted into Standard Uptake Values (SUVs). Compared to the control group, the uptake of FDG in the cerebellum was significantly decreased in both the low and high dose groups. These preliminary data demonstrate that microPET imaging is capable of distinguishing differences in retention of FDG in the brains of NHPs treated chronically with MPH and suggests that this approach may provide a minimally invasive biomarker for exploring the effects of chronic MPH treatment on aspects of brain function.
National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079, United States.
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X
Zhang
National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079, United States.
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GD
Newport
Animal Resource Center, UT Southwestern Medical Center, Dallas, Texas, United States.
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R
Callicott
National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079, United States.
S
S
Liu
National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079, United States.
J
J
Thompson
3D Imaging, LLC, Little Rock, AR 72113, United States; University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
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MS
Berridge
3D Imaging, LLC, Little Rock, AR 72113, United States; University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
S M
SM
Apana
National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079, United States.
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W
Slikker
National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079, United States.
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C
Wang
National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079, United States.
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MG
Paule
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage*; D049268:Positron-Emission Tomography; D014057:Tomography, X-Ray Computed
D000697:Central Nervous System Stimulants; D019788:Fluorodeoxyglucose F18; D008774:Methylphenidate
ADHD; FDG; In vivo; Methylphenidate; MicroPET/CT; Nonhuman primates