Carbon-11-labeled KF15372: a potential central nervous system adenosine A1 receptor ligand.
The carbon-11-labeled selective adenosine A1 antagonist KF15372 ([1-propyl-11C]8-dicyclopropylmethyl-1,3-dipropylxanthine) was elevated in vivo as a PET ligand for mapping CNS adenosine A1 receptors.


METHODS
The regional brain distribution of [11C]KF15372 and the effects of adenosine antagonists on the distribution were determined in mice by tissue sampling. In rats, in which the retinal projection fibres to the superior colliculus had degenerated due to unilateral eye removal, the brain distribution of [11C]KF15372 was visualized by ex vivo autoradiography.


RESULTS
The mouse brain uptake of [11C]KF15372 was 1.8% i.d./g at 5 min and then it gradually decreased. The uptake was high in the hippocampus, cerebral cortex, striatum and cerebellum, and was significantly reduced by A1 antagonists but not by A2 antagonists. The brain distribution of 11C assessed by the tissue sampling and autoradiography was compatible with that of the A1 receptors. Autoradiography clearly visualized unilaterally decreased A1 receptor binding in the superior colliculus.


CONCLUSIONS
The results demonstrated that [11C]KF15372 is a selective and high-affinity adenosine A1 receptor ligand and is useful for detecting the degeneration of presynaptic neurons.
Furuta
R
R
Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Japan.
Ishiwata
K
K
Kiyosawa
M
M
Ishii
S
S
Saito
N
N
Shimada
J
J
Endo
K
K
Suzuki
F
F
Senda
M
M
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D015353:Eye Enucleation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009410:Nerve Degeneration; D017729:Presynaptic Terminals / Q000378:metabolism / Q000502:physiology; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000187:drug effects*; D014018:Tissue Distribution; D014970:Xanthines / Q000493:pharmacokinetics
D002250:Carbon Radioisotopes; D011983:Receptors, Purinergic; D014970:Xanthines; C067197:8-(dicyclopropylmethyl)-1,3-dipropylxanthine