MicroPET/CT assessment of FDG uptake in brain after long-term methylphenidate treatment in nonhuman primates

Area of Science:

• Neuroscience
• Pharmacology
• Medical Imaging

Background:

• Methylphenidate (MPH) is a common psychostimulant for Attention-Deficit Hyperactivity Disorder (ADHD).
• Long-term effects of MPH on the central nervous system (CNS) remain incompletely understood.
• Non-human primates (NHPs) offer a valuable model for studying chronic drug effects on brain function.

Purpose of the Study:

• To investigate the long-term effects of methylphenidate (MPH) on brain metabolism in young adult male rhesus monkeys.
• To utilize [(18)F]Fluoro-2-deoxy-2-d-glucose (FDG) positron emission tomography/computed tomography (microPET/CT) imaging as a biomarker for MPH-induced changes.
• To assess dose-dependent effects of chronic MPH administration on regional brain glucose uptake.

Main Methods:

• Young adult male rhesus monkeys (n=4/group) received oral MPH (2.5 or 12.5mg/kg/dose) or vehicle for 6 years.
• MicroPET/CT scans were performed on Mondays, approximately 68 hours after the last MPH dose, to minimize acute drug effects.
• FDG uptake was measured in regions of interest including the prefrontal cortex, temporal cortex, striatum, and cerebellum, converted to Standard Uptake Values (SUVs).

Main Results:

• Chronic MPH treatment, at both low and high doses, resulted in a significant decrease in FDG uptake in the cerebellum compared to controls.
• MicroPET/CT imaging successfully distinguished differences in FDG retention in the brains of NHPs exposed to chronic MPH.
• No significant changes were observed in other brain regions examined (prefrontal cortex, temporal cortex, striatum) in this preliminary study.

Conclusions:

• MicroPET/CT imaging with FDG can detect alterations in brain metabolism associated with chronic methylphenidate (MPH) exposure in non-human primates.
• The observed decrease in cerebellar FDG uptake suggests a potential neurobiological effect of long-term MPH treatment.
• This imaging approach may serve as a minimally invasive biomarker for evaluating the long-term impact of MPH on brain function.