ABSTRACT
With [11C]raclopride,[11C]nemonapride and [11C]N-methylspiperone, degeneration of dopamine D2-like receptors in the unilaterally quinolinic acid-lesioned rats was evaluated by positron emission tomography (PET) and ex vivo and in vitro autoradiography. PET showed a decreased uptake of [11C]raclopride in the lesioned striatum, but an increased uptake of [11C]nemonapride and [11C]N-methylspiperone despite a decreased binding in vitro. Ex vivo autoradiography showed an increased accumulation of the three ligands in the cortical region overlying the injured striatum, probably enlarging PET signals. PET has the limited potential for evaluating the receptor degeneration in the present animal model.
Subject(s)
Benzamides/pharmacokinetics , Dopamine Antagonists/pharmacokinetics , Neostriatum/metabolism , Neurotoxins/toxicity , Quinolinic Acid/toxicity , Raclopride/pharmacokinetics , Radiopharmaceuticals/pharmacokinetics , Receptors, Dopamine D2/metabolism , Spiperone/analogs & derivatives , Spiperone/pharmacokinetics , Tomography, Emission-Computed/methods , Animals , Autoradiography , Glucose/metabolism , Magnetic Resonance Imaging , Male , Neostriatum/drug effects , Rats , Rats, Wistar , Receptors, Dopamine D2/drug effects , Receptors, GABA-A/metabolismABSTRACT
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.