嘧啶二价阴离子的选择性烷基化III：[11C-甲基]-胸苷的无载体添加合成

Selective alkylation of pyrimidyl dianions III: no-carrier-added synthesis of [11C-methyl]-thymidine.

作者信息

Alauddin M M, Ravert H T, Musachio J L, Mathews W B, Dannals R F, Conti P S

机构信息

PET Imaging Science Center University of Southern California, School of Medicine Los Angeles, CA 90033, USA.

出版信息

Nucl Med Biol. 1995 Aug;22(6):791-4. doi: 10.1016/0969-8051(95)00027-u.

DOI:10.1016/0969-8051(95)00027-u

PMID:8535340

Abstract

A no-carrier-added, high specific activity synthesis of [11C-methyl]-thymidine is reported. Reaction of 3'. 5'-O-bis-(tetrahydropyramyl)-5-bromo-2'-deoxyuridine with n-butylithium produced a diamion which was alkylated with [11C]-methyl iodide, and on subsequent hydrolysis, yielded [IIC-methyl]-thymidine. The labeled compound was isolated from the by-product 2'-deoxymidine by HPLC on a reverse phase C18 semipreparative column with mean radiochemical yield of 18.8% (decay corrected) in 30-35 min and radiochemical purity >99%. This no-carrier-added synthesis can be used to produce [11C-methyl]-thymidine with mean specific activity over 1000 mCi/mumol for positron emission tomography (PET) studies.

摘要

报道了一种无载体添加的高比活度[¹¹C-甲基]-胸苷的合成方法。3',5'-O-双-(四氢吡喃基)-5-溴-2'-脱氧尿苷与正丁基锂反应生成二胺，该二胺用[¹¹C]-甲基碘进行烷基化反应，随后水解得到[¹¹C-甲基]-胸苷。通过在反相C18半制备柱上进行高效液相色谱法，从副产物2'-脱氧胸苷中分离出标记化合物，在30 - 35分钟内平均放射化学产率为18.8%（衰变校正），放射化学纯度>99%。这种无载体添加的合成方法可用于生产用于正电子发射断层扫描（PET）研究的平均比活度超过1000 mCi/μmol的[¹¹C-甲基]-胸苷。