Occupancy of adenosine A2A receptors by istradefylline in patients with Parkinson's disease using 11C-preladenant PET

Istradefylline, an adenosine A(2A) receptor (A(2A)R) antagonist, is effective as an adjunct to levodopa and can alleviate "off" time and motor symptoms in patients with Parkinson's disease (PD). The present study aimed to calculate occupancy rates of A(2A)Rs by administrating istradefylline 20 mg or 40 mg, which is the currently approved dose for PD in Japan. Additionally, A(2A)R availability was compared between patients with PD and healthy controls. Ten patients with PD under levodopa therapy and six age-matched healthy controls were included. The patients underwent a total of two C-11-preladenant positron emission tomography scans before and after the administration of istradefylline 20 mg or 40 mg (both n = 5). Binding potential (BPND) was calculated to estimate A(2A)R availability in the ventral striatum, caudate, and putamen. Maximal A(2A)R occupancy and ED50 were estimated by modeling the dose-occupancy curves. All patients were around the middle stage of PD, and their characteristics were clinically heterogeneous. Maximal A(2A)R occupancy and ED50 were 93.5% and 28.6 mg in the ventral striatum, 69.5% and 10.8 mg in the caudate, and 66.8% and 14.8 mg in the putamen, respectively. There were no significant differences in BEN. values in the ventral striatum (P = 0.42), caudate (P = 0.72), and putamen (P = 0.43) between the PD and control groups. In conclusion, the present study shows that istradefylline binds to A(2A)Rs dose-dependently. A sufficient occupancy of A(2A)Rs could be obtained by administrating the approved dose of istradefylline.