Radiolabeled Guanine Derivatives for the in Vivo Mapping of O6-Alkylguanine-DNA Alkyltransferase: 6-(4-[18F]Fluoro-benzyloxy)-9H-purin-2-ylamine and 6-(3-[131<

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• 作者：Ganesan Vaidyanathan ; Donna J. Affleck ; Christina M. Cavazos ; Stewart P. Johnson ; Sriram Shankar ; Henry S. Friedman ; Michael O. Colvin ; and Michael R. Zalutsky
• 刊名：Bioconjugate Chemistry
• 出版年：2000
• 出版时间：November 2000
• 年：2000
• 卷：11
• 期：6
• 页码：868 - 875
• 全文大小：96K
• 年卷期：v.11,no.6(November 2000)
• ISSN：1520-4812

文摘

Two radiolabeled analogues of 6-benzyloxy-9H-purin-2-ylamine (O⁶-benzylguanine; BG) potentiallyuseful in the in vivo mapping of O⁶-alkylguanine-DNA alkyltransferase (AGT) were synthesized.Fluorine-18 labeling of the known 6-(4-fluoro-benzyloxy)-9H-purin-2-ylamine (FBG; 6) was accomplished by the condensation of 4-[¹⁸F]fluorobenzyl alcohol with 2-aminopurin-6-yltrimethylammonium chloride (4) or 2-amino-6-chloropurine in average decay-corrected radiochemical yields of40 and 25%, respectively. Unlabeled 6-(3-iodo-benzyloxy)-9H-purin-2-ylamine (IBG; 7) was preparedfrom 4 and 3-iodobenzyl alcohol. Radioiodination of 9, prepared from 7 in two steps, and subsequentdeprotection gave [¹³¹I]7 in about 70% overall radiochemical yield. The IC₅₀ values for the inactivationof AGT from CHO cells transfected with pCMV-AGT were 15 nM for IBG and 50 nM for FBG. Thebinding of [¹⁸F]6 and [¹³¹I]7 to purified AGT was specific and saturable with both exhibiting similarIC₅₀ values (5-6 M).