Chappell L L, Rogers B E, Khazaeli M B, Mayo M S, Buchsbaum D J, Brechbiel M W
Radioimmune and Inorganic Chemistry Section, DCS, NCI, NIH, Bethesda, MD 20892, USA.
Bioorg Med Chem. 1999 Nov;7(11):2313-20. doi: 10.1016/s0968-0896(99)00171-6.
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.
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。
