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

We proposed [C-11]KF18446 as a selective radioligand for mapping the adenosine A(2A) receptors being highly enriched in the striatum by positron emission tomography (PET). In the present study, we investigated whether [ I I C] KF 18446 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 [C-11]KF18446. The extent of the striatal lesion was identified based on MRI, to which the PET was co-registered. The binding potential of [C-11]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 D-2 receptors in the lesioned striatum, but seemed to be larger than the decrease in the potential of [C-11]SCH 23390 binding to dopamine D-1 receptors. Ex vivo and in vitro autoradiography validated the PET signals. We concluded that (C-11]KF18446 PET can detect change in the adenosine A(2A) receptors in the rat model, and will provide a new diagnostic tool for characterizing post-synaptic striatopallidal neurons in the stratum.