Age-Related Decrease in Male Extra-Striatal Adenosine A1 Receptors Measured Using 11C-MPDX PET

Adenosine A(1) receptors (A(1)Rs) are widely distributed throughout the entire human brain, while adenosine A(2A) receptors (A(2A)Rs) are present in dopamine-rich areas of the brain, such as the basal ganglia. A past study using autoradiography reported a reduced binding ability of A(1)R in the striatum of old rats. We developed positron emission tomography (PET) ligands for mapping the adenosine receptors and we successfully visualized the A(1)Rs using 8-dicyclopropylmethyl-1-C-11-methyl-3-propylxanthine (C-11-MPDX). We previously reported that the density of A(1)Rs decreased with age in the human striatum, although we could not observe an age-related change in A(2A)Rs. The aim of this study was to investigate the age-related change of the density of A(1)Rs in the thalamus and cerebral cortices of healthy participants using C-11-MPDX PET. We recruited eight young (22.0 +/- 1.7 years) and nine elderly healthy male volunteers (65.7 +/- 8.0 years). A dynamic series of decay-corrected PET scans was performed for 60 min starting with the injection of C-11-MPDX. We placed the circular regions of interest of 10 mm in diameter in C-11-MPDX PET images. The values for the binding potential (BPND) of C-11-MPDX in the thalamus, and frontal, temporal, occipital, and parietal cortices were calculated using a graphical analysis, wherein the reference region was the cerebellum. BPND of C-11-MPDX was significantly lower in elderly participants than young participants in the thalamus, and frontal, temporal, occipital, and parietal cortices. In the human brain, we could observe the age-related decrease in the distribution of A(1)Rs.