Adenosine A(1) receptors using 8-dicyclopropylmethyl-1-[(11)C]methyl-3-propylxanthine PET in Alzheimer's disease.
OBJECTIVE
Adenosine is an endogenous modulator of synaptic functions in the central nervous system. The effects of adenosine are mediated by at least four adenosine receptor subtypes. Decreased density of adenosine A1 receptors, which is a major subtype adenosine receptor in the hippocampus, has been reported in vitro in Alzheimer's disease. We evaluated adenosine A1 receptor in the brain of elderly normal subjects and patients with Alzheimer's disease (n = 8 and 6, respectively), using positron emission tomography (PET) and 8- dicyclopropylmethyl-1-[(11)C]methyl-3-propylxanthine ([(11)C]MPDX).


METHODS
A 60-min PET scan with [(11)C]MPDX was performed. The patients with Alzheimer's disease also underwent PET with [(18)F]fluorodeoxyglucose (FDG). The binding potential of [11C]MPDX was quantitatively calculated in the regions of interest (ROIs) placed on the frontal, medial frontal, temporal, medial temporal, parietal, and occipital cortices, striatum, thalamus, cerebellum, and pons. Statistical parametric mapping (SPM2) was used for analysis of [(11)C]MPDX and FDG-PET.


RESULTS
In the ROI-based analysis, the binding potential of [(11)C]MPDX in patients with Alzheimer's disease was significantly lower in the temporal and medial temporal cortices and thalamus than that in elderly normal subjects (P = 0.038, 0.028, and 0.039, respectively). SPM analysis also showed significant decreased binding potential in the temporal and medial temporal cortices and thalamus in patients with Alzheimer's disease. FDG uptake was significantly decreased in the temporoparietal cortex and posterior cingulate gyrus.


CONCLUSIONS
Decreased binding of [(11)C]MPDX in patients with Alzheimer's disease was detected in temporal and medial temporal cortices and thalamus. This pattern possibly differed from the hypometabolism pattern of FDG. [(11)C]MPDX PET is valuable for the detection of degeneration in the temporal and medial temporal cortices and corticothalamic transmission, and may provide a different diagnostic tool from FDG-PET in brain disorders such as Alzheimer's disease.
Fukumitsu
Nobuyoshi
N
Proton Medical Research Center, University of Tsukuba, Ibaraki, Japan. fukumitsun@yahoo.co.jp
Ishii
Kenji
K
Kimura
Yuichi
Y
Oda
Keiichi
K
Hashimoto
Masaya
M
Suzuki
Masahiko
M
Ishiwata
Kiichi
K
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D014970:Xanthines / Q000493:pharmacokinetics*
C451639:1-methyl-8-dicyclopropylmethyl-1-methyl-3-propylxanthine; D019275:Radiopharmaceuticals; D043682:Receptor, Adenosine A1; D014970:Xanthines