Objective: To determine the effect of dopaminergic medication on Adenosine 2A (A2A) receptor availability in patients with Parkinson’s disease (PD).

Background: A2A receptors form a heterodimer with dopamine D2 receptors on the medium spiny neurons of the indirect pathway in basal ganglia. Previous in-vivo PET studies have shown an increase in A2A receptor binding in late stage PD patients with dyskinesia. A2A antagonists, such as istradefylline, help in reducing ‘off time’ when taken as an adjunctive medication to levodopa/carbidopa. There is, however, a lack of understanding of how dopaminergic medication may affect the availability of A2A receptors in-vivo and hence, the possible mechanism of action of A2A antagonists in earlier stages as well as in the dyskinetic phase of the disease.

Design/Methods: Eight PD patients with (mean age 67.9 years, mean disease duration 5.0 years) without dyskinesia were enrolled. A2A receptor availability was measured using PET imaging with radioligand [11C]TMSX after short term cessation of dopaminergic medication (12 hrs for levodopa, 24 hrs for dopamine agonists and MAO-B inhibitors). Repeated PET imaging was performed while the patients were on their regular dopaminergic medication (mean 30 days after first imaging). Conventional MRI was acquired for anatomical reference. An in-house developed brain image processing pipeline was used for normalization, segmentation and kinetic modeling to calculate distribution volume ratio (DVR) in 3 striatal and 15 extra-striatal regions of interest. Statistical analysis was performed using GraphPad Prism (version 8.2).

Results: No significant differences between [11C]TMSX binding without and during dopaminergic medication were observed in any of the brain regions (p=0.19). Significantly effective pairing was found between the “on” and “off” medication states (Pearson’s r=0.954, p<0.001). Intraclass Correlation Coefficient was also high (0.987) representing strong association.

Conclusions: Our results show that dopaminergic medication has no short-term effect on the availability of A2A receptors in patients with PD.