Adenosine A2A receptor imaging with [11C]KF18446 PET in the rat brain after quinolinic acid lesion: Comparison with the dopamine receptor imaging

Abstract

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.

Regional and subtype selective changes of neurotransmitter receptor density in a rat transgenic for the Huntington's disease mutation

“…Most significant losses were detected in the dopaminergic (D 1 and D 2 receptors) and adenosinergic (A 2A receptor) receptor systems. These findings are in good accordance with human post-mortem studies (Glass et al 2000) that have been confirmed by in vivo PET studies, which clearly demonstrate a massive loss of D 2 dopamine (Turjanski et al 1995;Ginovart et al 1997;Antonini et al 1998;Araujo et al 2000;Pavese et al 2003) and A 2A adenosine (Ishiwata et al 2002) receptors, respectively. A reduction of NMDA receptor density, which has been described in the putamen of HD patients (Young et al 1988), could not be confirmed.…”

Type 1 cannabinoid receptor mapping with [18F]MK-9470 PET in the rat brain after quinolinic acid lesion: a comparison to dopamine receptors and glucose metabolism

“…In patients and animals with HD, metabolic abnormalities and reductions in dopamine binding are well described in striatal and extrastriatal regions, progressively decreasing upon symptom severity [18,19,[41][42][43][44][45]. Here, [ 18 F]FDG values of the caudate-putamen were higher than, but positively correlated to D 2 impairment.…”

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

“…It is also possible that the expression of A 2A Rs might also increase in animal models and patients with Huntington's disease, since the expression of A 2A Rs is increased in neurons over-expressing huntingtin [213]. However, the major loss of medium spiny neurons in this condition may mask the increased density of A 2A Rs in the remaining viable neurons [211,214,215]. Interestingly, this idea that brain A 2A Rs might be up-regulated by noxious stimuli was most evident in a recent study focusing on extra-striatal regions.…”