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]fluoroe

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• 作者：Schirrmacher ; Ralf ; Nesseler ; Esther ; Hamkens ; Wilhelm ; Eichhorn ; Uta ; Schreckenberger ; Mathias ; et. al.
• 关键词：MGMT ; Alkyltransferase ; 6-benzyloxy-9H-purin-2-ylamine
• 刊名：Applied Radiation and Isotopes
• 出版年：2002
• 期刊代码：6_09698043
• 类别：ce
• 出版时间：March, 2002
• 卷：56
• 期：3
• 页码：511-517
• 文件大小：121 K

摘要

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 O⁶-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 1.8μM. 6-benzyloxy-9-(2-[¹⁸F]fluoroethyl)-9H-purin-2-yl-amine and 6-benzyloxy-7-(2-[¹⁸F]fluoroethyl)-7H-purin-2-yl-amine were synthesized by alkylation of 6-benzyloxy-9H-purin-2-ylamine with 1-[¹⁸F]fluoro-2-tosylethane in optimized yields of 41%and 20%, respectively. Biodistribution studies were performed in nude mice, carrying mex+ (MGMT expressing) and mex− tumors.