title: 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).
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.
authors.affiliation: Radioimmune and Inorganic Chemistry Section, DCS, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: L L
authors.initials: LL
authors.lastname: Chappell
authors.forename: B E
authors.initials: BE
authors.lastname: Rogers
authors.forename: M B
authors.initials: MB
authors.lastname: Khazaeli
authors.forename: M S
authors.initials: MS
authors.lastname: Mayo
authors.forename: D J
authors.initials: DJ
authors.lastname: Buchsbaum
authors.forename: M W
authors.initials: MW
authors.lastname: Brechbiel
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000532:radiotherapy; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D004195:Disease Models, Animal; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D008187:Lutetium / Q000737:chemistry / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy
chemical_list: D000814:Aniline Compounds; D002614:Chelating Agents; D003432:Cross-Linking Reagents; D006571:Heterocyclic Compounds; C085738:4-aminophenylethyl-1,4,7,10-tetraazacyclodecane-N,N',N'',N'''-tetraacetic acid; D008187:Lutetium