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[ 11 C]Preladenant was developed as a novel adenosine A 2A receptor positron emission tomography radioligand. The present study aims to evaluate the suitability of [ 11 C]preladenant positron emission tomography for the quantification of striatal A 2A receptor density and the assessment of striatal A 2A receptor occupancy by KW-6002. Sixty- or ninety-minute dynamic positron emission tomography imaging was performed on rats. Tracer kinetics was quantified by the two-tissue compartment model, Logan graphical analysis and several reference tissue-based models. Test-retest reproducibility was assessed by repeated imaging on two consecutive days. Two-tissue compartment model and Logan plot estimated comparable distribution volume ( V T ) values of ∼10 in the A 2A receptor-rich striatum and substantially lower values in all extra-striatal regions (∼1.5-2.5). The simplified reference tissue model with midbrain or occipital cortex as the reference region proved to be the best non-invasive model for quantification of A 2A receptor, showing a striatal binding potential ( BP ND ) value of ∼5.5, and a test-retest variability of ∼5.5%. The brain metabolite analysis showed that at 60-min post injection, 17% of the radioactivity in the brain was due to radioactive metabolites. The ED 50 of KW-6002 in rat striatum for i.p. injection was 0.044-0.062 mg/kg. The study demonstrates that [ 11 C]preladenant is a suitable tracer to quantify striatal A 2A receptor density and assess A 2A receptor occupancy by A 2A receptor-targeting molecules.

journal of cerebral blood flow and metabolism

In vivo evaluation of [<sup>11</sup>C]preladenant positron emission tomography for quantification of adenosine A<sub>2A</sub> receptors in the rat brain

In vivo evaluation of [11C]preladenant positron emission tomography for quantification of adenosine A2A receptors in the rat brain

In vivo evaluation of [¹¹C]preladenant positron emission tomography for quantification of adenosine A_2A receptors in the rat brain