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双功能螯合剂1,4,7,10-四氮杂-N-(1-羧基-3-(4-硝基苯基)丙基)-N',N'',N'''-三(乙酸)环十二烷(PA-DOTA)的改进合成方法。

Improved synthesis of the bifunctional chelating agent 1,4,7,10-tetraaza-N-(1-carboxy-3-(4-nitrophenyl)propyl)-N',N'',N'''-tri s(acetic acid)cyclododecane (PA-DOTA).

作者信息

Chappell L L, Rogers B E, Khazaeli M B, Mayo M S, Buchsbaum D J, Brechbiel M W

机构信息

Radioimmune and Inorganic Chemistry Section, DCS, NCI, NIH, Bethesda, MD 20892, USA.

出版信息

Bioorg Med Chem. 1999 Nov;7(11):2313-20. doi: 10.1016/s0968-0896(99)00171-6.

DOI:10.1016/s0968-0896(99)00171-6

PMID:10632041

Abstract

A concise synthesis of the bifunctional chelating agent 1,4,7,10-tetraaza-N-(1-carboxy-3-(4-nitrophenyl)propyl)-N',N'',N'' '-tris(acetic acid)cyclododecane (PA-DOTA) is reported. Difficulties involving the production of partially alkylated products and their removal have been addressed and obviated. After the pure nitro form of PA-DOTA was obtained, conversion to the isothiocyanato form PA-DOTA (1, conjugation to HuCC49 and HuCC49deltaCH2 monoclonal antibodies was achieved. Subsequent radiolabeling with 177Lu was performed, demonstrating a useful bifunctional chelating agent suitable for clinical radioimmunotherapy applications.

摘要

报道了双功能螯合剂1,4,7,10-四氮杂环十二烷-N-(1-羧基-3-(4-硝基苯基)丙基)-N',N'',N'' '-三(乙酸)(PA-DOTA)的简洁合成方法。解决并避免了涉及部分烷基化产物的生成及其去除的难题。在获得PA-DOTA的纯硝基形式后，将其转化为异硫氰酸酯形式的PA-DOTA(1)，实现了与HuCC49和HuCC49deltaCH2单克隆抗体的偶联。随后用177Lu进行放射性标记，证明该双功能螯合剂适用于临床放射免疫治疗应用。