Improved 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)

A concise synthesis of the bifunctional chelating agent 1,4,7,10- tetraaza-N-(1-carboxy-3-(4-nitrophenyl)propyl)-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 HuCC49ΔCH2 monoclonal antibodies was achieved. Subsequent radiolabeling with ¹⁷⁷Lu was performed, demonstrating a useful bifunctional chelating agent suitable for clinical radioimmunotherapy applications. (C) 1999 Published by Elsevier Science Ltd.