Preparation and primary evaluation of [C-11]CSC as a possible tracer for mapping adenosine A(2A) 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 reacti on of (E)-8-(3-chlorostyryl)-1,3,-dimethylxanthine and [C-11]methyl iodide. The decay-corrected radiochemical yield was 32.3% with a radiochemical pur ity of 99%, a specific activity of 1.85-5.55 GBq/mu mol and a preparation t ime of 1 h. A primary evaluation of [C-11]CSC as a potential tracer for map ping 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 uptak e 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 st riatum, in accordance with previous findings on the specific spatial distri bution of A(2A) adenosine receptors and also in the medulla oblongata. Dyna mic PET studies on rabbits showed a fast brain uptake of CSC, reaching a ma ximum 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 r eceptor. (C) 1999 Elsevier Science Ltd. All rights reserved.