Synthesis of 2-[11C]methoxy-3,17β-estradiol to measure the pharmacokinetics of an antitumor drug candidate, 2-methoxy-3,17β-estradiol

2-Methoxy-3,17 beta-estradiol, an endogenous estrogen metabolite, showed cytotoxicity in various cancer cell lines and also has antiangiogenic and proapoptotic activities. Clinical I and 11 trials of 2-methoxy-3,17 beta-estradiol for multiple myeloma, advanced solid tumors, metastatic breast and prostate cancer are underway. We prepared 2-[C-11]methoxy-3,17 beta-estradiol to measure the pharmacokinetics and organ distribution of 2-methoxy-3,17 beta-estradiol in clinical trials. 2-[C-11]Methoxy-3,17 beta-estradiol was synthesized from a precursor, 2-hydroxy-3,17 beta-O-bis(methoxymethyl)estradiol, in two steps with over 99% radiochemical purity. The overall reaction time was 45 min and the decay-corrected radiochemical yield was 32.9%. The distribution coefficient (logP(7.4)) of 2-[C-11]methoxy-3,17 beta-estradiol at pH 7.4 was measured as 2.95. Copyright (c) 2006 John Wiley & Sons, Ltd.