Preparation and primary evaluation of [11C]CSC as a possible tracer for mapping adenosine A2A receptors by PET

A C-11 labeled selective adenosine A(2A) antagonist, (E)-8-(3-chlorostyryl)-1,3-dimethyl-7-[C-11]methylxanthine ([C-11]CSC) was prepared by the reaction of (E)-8-(3-chlorostyryl)-1,3,-dimethylxanthine and [C-11]methyl iodide. The decay-corrected radiochemical yield was 32.3% with a radiochemical purity of 99%, a specific activity of 1.85-5.55 GBq/mu mol and a preparation time of 1 h. A primary evaluation of [C-11]CSC as a potential tracer for mapping adenosine AZA receptors by positron emission tomography (PET) is also presented. Biodistribution and autoradiographic studies were carried out on Swiss mice and domestic rabbits. In mice the lung showed the highest uptake at 10 min after i.v. injection, followed by the liver, kidney, heart and brain. Inside the brain a high level of radioactivity accumulated in the striatum, in accordance with previous findings on the specific spatial distribution of A(2A) adenosine receptors and also in the medulla oblongata. Dynamic PET studies on rabbits showed a fast brain uptake of CSC, reaching a maximum in less then 2 min. On the basis of competition experiments with the unlabeled ligand [C-11]CSC proves to bind specifically to the appropriate receptor. (C) 1999 Elsevier Science Ltd. All rights reserved.