In vivo imaging of adenosine A1 receptors in the human brain with [18F]CPFPX and positron emission tomography.
The important roles played by the A(1) adenosine receptor (A(1)AR) in brain physiology and pathology make this receptor a target for in vivo imaging. Here we describe the distribution of A(1)ARs in the living human brain with PET, made possible for the first time by the highly potent and selective A(1)AR antagonist 8-cyclopentyl-3-(3-[(18)F]fluoropropyl)-1-propylxanthine ([(18)F]CPFPX). In vivo data demonstrate a rapid cerebral uptake, peaking at 2.9 +/- 0.6% injected dose/liter at 3.3 +/- 1.3 min, followed by a gradual washout. Consistent with the results of autoradiography, high receptor densities occurred in the putamen and the mediodorsal thalamus. Neocortical regions showed regional differences in [(18)F]CPFPX binding, with high accumulation in temporal > occipital > parietal > frontal lobes and a lower level of binding in the sensorimotor cortex. Ligand accumulation was low in cerebellum, midbrain, and brain stem. Metabolism of [(18)F]CPFPX is rapid outside the central nervous system, but the metabolites do not penetrate the blood-brain barrier. In conclusion, in vivo application of [(18)F]CPFPX, a highly potent and selective PET ligand, for the first time allows the imaging of A(1)ARs in the living human brain.
Bauer
Andreas
A
Institute of Medicine, Research Center Jülich, D-52425 Jülich, Germany. an.bauer@fz-juelich.de
Holschbach
Marcus H
MH
Meyer
Philipp T
PT
Boy
Christian
C
Herzog
Hans
H
Olsson
Ray A
RA
Coenen
Heinz H
HH
Zilles
Karl
K
D000328:Adult; D001345:Autoradiography / Q000379:methods; D001812:Blood-Brain Barrier / Q000502:physiology; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008297:Male; D020645:Mediodorsal Thalamic Nucleus / Q000000981:diagnostic imaging / Q000473:pathology; D008875:Middle Aged; D019579:Neocortex / Q000000981:diagnostic imaging / Q000473:pathology; D011699:Putamen / Q000000981:diagnostic imaging / Q000473:pathology; D018047:Receptors, Purinergic P1 / Q000032:analysis*; D012016:Reference Values; D014055:Tomography, Emission-Computed / Q000379:methods*; D014970:Xanthines / Q000493:pharmacokinetics
C468796:8-cyclopenta-3-(3-fluoropropyl)-1-propylxanthine; D005462:Fluorine Radioisotopes; D018047:Receptors, Purinergic P1; D014970:Xanthines