Adenosine A2A receptor imaging with [11C]KF18446 PET in the rat brain after quinolinic acid lesion: comparison with the dopamine receptor imaging.
We proposed [11C]KF18446 as a selective radioligand for mapping the adenosine A2A receptors being highly enriched in the striatum by positron emission tomography (PET). In the present study, we investigated whether [11C]KF18446 PET can detect the change in the striatal adenosine A2A receptors in the rat after unilateral injection of an excitotoxin quinolinic acid into the striatum, a Huntington's disease model, to demonstrate the usefulness of [11C]KF18446. The extent of the striatal lesion was identified based on MRI, to which the PET was co-registered. The binding potential of [11C]KF18446 significantly decreased in the quinolinic acid-lesioned striatum. The decrease was comparable to the decrease in the potential of [11C]raclopride binding to dopamine D2 receptors in the lesioned striatum, but seemed to be larger than the decrease in the potential of [11C]SCH 23390 binding to dopamine D1 receptors. Ex vivo and in vitro autoradiography validated the PET signals. We concluded that [11C]KF18446 PET can detect change in the adenosine A2A receptors in the rat model, and will provide a new diagnostic tool for characterizing post-synaptic striatopallidal neurons in the stratum.
Ishiwata
Kiichi
K
Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Japan. ishiwata@pet.tmig.or.jp
Ogi
Nobuo
N
Hayakawa
Nobutaka
N
Oda
Keiichi
K
Nagaoka
Tsukasa
T
Toyama
Hinako
H
Suzuki
Fumio
F
Endo
Kazutoyo
K
Tanaka
Akira
A
Senda
Michio
M
D000818:Animals; D001345:Autoradiography; D001552:Benzazepines / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D006816:Huntington Disease / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D017378:Quinolinic Acid; D020891:Raclopride / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A; D011954:Receptors, Dopamine / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D012016:Reference Values; D014055:Tomography, Emission-Computed / Q000379:methods; D014970:Xanthines / Q000493:pharmacokinetics*
D001552:Benzazepines; D002250:Carbon Radioisotopes; C405422:KF18446; D019275:Radiopharmaceuticals; D043705:Receptor, Adenosine A2A; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D018047:Receptors, Purinergic P1; D014970:Xanthines; D020891:Raclopride; D017378:Quinolinic Acid