In vivo imaging of adenosine A2A receptors in rat and primate brain using [11C]SCH442416

Purpose: The aim of this study was to evaluate the suitability of [ ¹¹C]SCH442416 for the in vivo imaging of adenosine A_2A receptors. Methods: In rats and Macaca nemestrina, we evaluated the time course of the cerebral distribution of [¹¹C]SCH442416. Furthermore, in rats we investigated the rate of metabolic degradation, the inhibitory effects of different drugs acting on adenosine or dopamine receptors and the modification induced by the intrastriatal administration of quinolinic acid (QA). Results: The rate of metabolic degradation of [¹¹C]SCH442416 in rats was slow; 60 min after tracer injection, more than 40% of total plasma activity was due to unmetabolised [¹¹C]SCH442416. At the time of maximum uptake, radioactive metabolites represented only 6% of total extractable activity in the cerebellum and less than 1% in the striatum. In the striatum, the region with the highest expression of A_2A receptors, the in vivo uptake of [ ¹¹C]SCH442416 was significantly reduced only by drugs acting on A_2A receptors or by QA, a neurotoxin that selectively reduces the number of intrastriatal GABAergic neurons. Position emission tomography (PET) studies in monkeys indicated that the tracer rapidly accumulates in brain, reaching maximum uptake between 5 and 10 min. Twenty minutes after the injection, radioactivity concentration in the striatum was two times that in the cerebellum. Conclusion: The specificity of binding, the rank order of regional distribution in the brain of rats and M. nemestrina, the good signal to noise ratios and the low amount of radioactive metabolites in brain and periphery indicate that [¹¹C]SCH442416 is a promising tracer for the in vivo imaging of A_2A adenosine receptors using PET. © Springer-Verlag 2004.