An approach to the evaluation of the activity of the DNA repair enzyme O6-methylguanine-DNA-methyl-transferase in tumor tissue in vivo:: syntheses of 6-benzyloxy-9-(2-[18F]fluoroethyl)-9H-purin-2-yl-amine and 6-benzyloxy-7-(2-[18F]fluoroethyl)-7H-purin-2-yl-amine

The resistance of tumor cells to the cytostatic activity of methylating and chloroethylating anticancer drugs is determined by the level of expression of the DNA repair protein O-6-methylguanine-DNA-methyl-transferase (MGMT). The synthesis of labelled 6-benzyloxy,-9H-purin-2-ylamine derivatives should hence allow a quantification of the MGMT status of tumor and non-target tissue in vivo. 6-benzyloxy-9-(2-fluoroethyl)-9H-purin-2-yl-amine and 6-benzyloxy-7-(2-fluoroethyl)-7H-purin-2- yl-amine were synthesized and evaluated in vitro, both showing an affinity, of 1.8muM, 6-benzyloxy-9-(2-[F-18]fluoroethyl)-9H-purin-2-yl-amine and 6-benzylox -7-(2-[F-18]fluoroethyl)-7H-purin-2-yl-amine were synthesized by alkylation of 6-benzyloxy -9H-Purin-2-ylamine with 1-[18F]flouro-2-tosylethane in optimized yields of 41%, and 20%. respectively. Biodistribution studies were performed in nude mice. carrying mex+ (MGMT expressing) and mex- tumors. (C) 2002 Elsevier Science Ltd. All rights reserved.