title: Synthesis, conjugation, and radiolabeling of a novel bifunctional chelating agent for (225)Ac radioimmunotherapy applications.
abstract: 225Ac (t(1/2) = 10 days) is an alternative alpha-emitter that has been proposed for radioimmunotherapy (RIT) due to its many favorable properties, such as half-life and mode of decay. The factor limiting use of (225)Ac in RIT is the lack of an acceptably stable chelate for in vivo applications. Herein is described the first reported bifunctional chelate for (225)Ac that has been evaluated for stability for in vivo applications. The detailed synthesis of a bifunctional chelating agent 2-(4-isothiocyanatobenzyl)-1,4,7,10,13, 16-hexaazacyclohexadecane- 1,4,7,10,13,16-hexaacetic acid (HEHA-NCS) is reported. This ligand was conjugated to three monoclonal antibodies, CC49, T101, and BL-3 with chelate-to-protein ratios between 1.4 and 2. The three conjugates were radiolabeled with (225)Ac, and serum stability study of the [(225)Ac]BL-3-HEHA conjugate was performed.
authors.affiliation: Radioimmune & Inorganic Chemistry Section, DCS, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: L L
authors.initials: LL
authors.lastname: Chappell
authors.forename: K A
authors.initials: KA
authors.lastname: Deal
authors.forename: E
authors.initials: E
authors.lastname: Dadachova
authors.forename: M W
authors.initials: MW
authors.lastname: Brechbiel
mesh_terms: D000186:Actinium; D000818:Animals; D001769:Blood; D002417:Cattle; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D018796:Immunoconjugates / Q000097:blood / Q000737:chemistry; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D016499:Radioimmunotherapy
chemical_list: D002614:Chelating Agents; D018796:Immunoconjugates; D008024:Ligands; D000186:Actinium