Acute Morphine Exposure Increases the Brain Distribution of [(18)F]DPA-714, a PET Biomarker of Glial Activation in Nonhuman Primates

BACKGROUND: The neuroinflammatory response to morphine exposure modulates its antinociceptive effects, tolerance, and dependence. Positron emission tomography radioligands for translocator protein-18kDa such as [(18)F]DPA-714 are noninvasive biomarkers of glial activation, a hallmark of neuroinflammation. METHODS: [(18)F]DPA-714 positron emission tomography imaging was performed in 5 baboons at baseline and 2 hours after i.m. morphine injection (1 mg/kg). Brain kinetics and metabolite-corrected input function were measured to estimate [(18)F]DPA-714 brain distribution. RESULTS: Morphine significantly increased [(18)F]DPA-714 brain distribution by a 1.3 factor (P<.05; paired t test). The effect was not restricted to opioid receptor-rich regions. Differences in baseline [(18)F]DPA-714 binding were observed among baboons. The response to morphine predominated in animals with the highest baseline uptake. CONCLUSIONS: [(18)F]DPA-714 positron emission tomography imaging may be useful to noninvasively investigate the brain immune component of morphine pharmacology. Correlation between baseline brain distribution and subsequent response to morphine exposure suggest a role for priming parameters in controlling the neuroinflammatory properties of opioids.