Striatal dopamine tone is positively associated with adiposity in humans as determined by PET using dual dopamine type-2 receptor antagonist tracers

The relationship between adiposity and dopamine type-2 receptor binding potential (D2BP) in the human brain has been repeatedly studied for >20 years with highly discrepant results, likely due to variable methodologies and differing study populations. We conducted a controlled inpatient feeding study to measure D2BP in the striatum using positron emission tomography with both [¹⁸F]fallypride and [¹¹C]raclopride in pseudo-random order in 54 young adults with a wide range of body mass index (BMI 20–44 kg/m²). Within-subject D2BP measurements using the two tracers were moderately correlated (r = 0.47, p < 0.001). D2BP was negatively correlated with BMI as measured by [¹¹C]raclopride (r = −0.51; p < 0.0001) but not [¹⁸F]fallypride (r = −0.01; p = 0.92) and these correlation coefficients were significantly different from each other (p < 0.001). Given that [¹⁸F]fallypride has greater binding affinity to dopamine type-2 receptors than [¹¹C]raclopride, which is more easily displaced by endogenous dopamine, our results suggest that adiposity is positively associated with increased striatal dopamine tone.ClinicalTrials.gov Identifier: NCT03648892