Adenosine A1 receptor mapping of the human brain by PET with 8-dicyclopropylmethyl-1-11C-methyl-3-propylxanthine.
Adenosine is an endogenous modulator of synaptic functions in the central nervous system. To investigate the physiologic and pathologic roles of the adenosine receptors in the human brain, PET is a powerful in vivo technique. In this study, we quantitatively evaluated the distribution of a major subtype A(1) adenosine receptor in the human brain by PET with a newly developed radioligand, 8-dicyclopropylmethyl-1-(11)C-methyl-3-propylxanthine ((11)C-MPDX).


METHODS
In 5 healthy volunteers, after PET measurement of the regional cerebral blood flow (rCBF) with (15)O-H(2)O, a 60-min PET scan with (11)C-MPDX was performed. The distribution volume (DV) of (11)C-MPDX was quantitatively evaluated by Logan's graphical analysis.


RESULTS
(11)C-MPDX was taken up at a high level, reaching a peak at 2-2.5 min, followed by a rapid decrease. The unchanged form of (11)C-MPDX in plasma was 75% at 60 min after injection. The DV of (11)C-MPDX was large in the striatum and thalamus, moderate in the cerebral cortices and pons, and small in the cerebellum. The distribution pattern of (11)C-MPDX in the brain was coincident with that of adenosine A(1) receptors in vitro, reported previously, but discretely different from that of rCBF.


CONCLUSIONS
(11)C-MPDX PET has the potential for mapping adenosine A(1) receptors in the human brain.
Fukumitsu
Nobuyoshi
N
Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. GZL13162@nifty.ne.jp
Ishii
Kenji
K
Kimura
Yuichi
Y
Oda
Keiichi
K
Sasaki
Toru
T
Mori
Yutaka
Y
Ishiwata
Kiichi
K
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D014018:Tissue Distribution; D014970:Xanthines / Q000493:pharmacokinetics*
C451639:1-methyl-8-dicyclopropylmethyl-1-methyl-3-propylxanthine; D019275:Radiopharmaceuticals; D043682:Receptor, Adenosine A1; D014970:Xanthines