S. Stoneelander et al., IN-VIVO BIODISTRIBUTION OF [N-C-11-METHYL]KF-17837 USING 3-D-PET - EVALUATION AS A LIGAND FOR THE STUDY OF ADENOSINE A(2A) RECEPTORS, Nuclear medicine and biology, 24(2), 1997, pp. 187-191
(KF 17837, ,4-dimethoxystyryl)-1,3-dipropyl-7-methylxanthine, was C-11
-labelled by methylation at N-7 of the nor-compound, KF 17440, using [
C-11]methyl iodide. Radiochemical conversions of 50% or 70-80% were ob
tained using sodium hydride or potassium carbonate, respectively, as b
ase. Total synthesis time was 40-45 min, including isolation by semipr
eparative liquid chromatography. Cerebral uptake of [N-C-11-methyl]KF
17837 in Cynomolgus monkeys, evaluated using positron emission tomogra
phy (PET), was so low that regional differences in distribution kineti
cs wtre revealed first after increasing injected dose 3-fold and using
3-D mode of data acquisition. At all times, the relative regional ret
ention (maximum striatum:cerebellum: cortex approximate to 1.1:1:0.8 a
t 20 min) was considerably different from the known relative density o
f A(2A) receptors in these regions. Radioactivity decreased more rapid
ly in the cortex than in the striatum and cerebellum (by 20% vs. 3-7%,
respectively, between 5 and 50 min). Addition of carrier to [N-C-11-m
ethyl]KF 17837 only marginally affected the cerebral radiotracer uptak
e. By contrast, in the heart the initial tracer uptake was high and th
e elimination kinetics was enhanced by adding unlabelled carrier. We h
ave thus shown that KF 17837 passes the blood-brain barrier, though to
a very low extent. This fact and the apparently high nonspecific bind
ing in vivo of [N-C-11-methyl]KF 17837 in regions with low receptor de
nsities limits its usefulness as a ligand for quantification of the ad
enosine A(2A) receptors in the primate brain. (C) 1997 Elsevier Scienc
e Inc.