Adenosine A1 receptors measured with 11C-MPDX PET in early Parkinson's disease

Adenosine A(1) receptors (A(1)Rs) interact negatively with dopamine D-1 receptors (D(1)Rs) in neurons of the basal ganglia's direct pathway, while adenosine A(2A) receptors (A(2A)Rs) negatively interact with dopamine D-2 receptors (D(2)Rs) in indirect-pathway neurons. The aim of this study was to investigate the cerebral density of A(1)Rs in Parkinson's disease (PD) in its early stages, using PET scans with the radioligand 8-dicyclopropylmethyl-1-C-11-methyl-3-propylxanthine (C-11-MPDX). We studied 10 drug-naive patients with early PD. Each patient was also examined for dopamine transporters (DATs) and D(2)Rs by PET using C-11-2--carbomethoxy-3--(4-fluorophenyl)-tropane (C-11-CFT) and C-11-raclopride (C-11-RAC), respectively. Ten elderly, healthy volunteers were recruited as controls for C-11-MPDX PET scanning and eight elderly volunteers were recruited as controls for C-11-CFT and C-11-RAC PET scanning. The PET scans revealed a decrease in the uptake ratio index (URI) of C-11-CFT and an increase in the URI of C-11-RAC in patients. In the temporal lobe, the binding potential for C-11-MPDX was higher in the patient group than in healthy subjects, but not in the other regions examined, including the striatum. In patients, we observed motor-symptom asymmetry and a relationship between parkinsonism and the striatal density of DATs, but not A(1)R density. In the putamen of early PD, asymmetrical down-regulation of A(2A)Rs is likely a compensatory mechanism in response to a decrease in dopamine. However, our study suggests that A(1)Rs are unaltered in the putamen of early PD.