title: Synthesis and evaluation of a macrocyclic bifunctional chelating agent for use with bismuth radionuclides.
abstract: The detailed synthesis of the bifunctional chelating agent 2-(p-isothiocyanatobenzyl)-1,4,7,10,13-pentaazacyclopentadecane-N,N',N",N"',N""-pentaacetic acid (BF_PEPA) is reported. This ligand was conjugated to monoclonal antibody B3 and the resultant immunoconjugate radiolabeled with (205,206)Bi. The in vivo stability of the radiolabeled immunoconjugate, and targeting characteristics were determined by biodistribution studies in A431 xenograft tumor-bearing mice sacrificed at 0.5, 1, 2, 4, and 24 hr. Results indicate that BF_PEPA appears to not be a suitable bifunctional chelating agent for sequestering isotopes of Bi(III) for radioimmunotherapy applications.
authors.affiliation: Radioimmune & Inorganic Chemistry Section, ROB, DCS, National Cancer Institute, Building 10, Room B3B69, 10 Center Drive, Bethesda, MD 20892-1002, USA.
authors.forename: K
authors.initials: K
authors.lastname: Garmestani
authors.forename: Z
authors.initials: Z
authors.lastname: Yao
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.forename: K
authors.initials: K
authors.lastname: Wong
authors.forename: C W
authors.initials: CW
authors.lastname: Park
authors.forename: I
authors.initials: I
authors.lastname: Pastan
authors.forename: J A
authors.initials: JA
authors.lastname: Carrasquillo
authors.forename: M W
authors.initials: MW
authors.lastname: Brechbiel
mesh_terms: D000818:Animals; D001729:Bismuth / Q000737:chemistry*; D002460:Cell Line; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000493:pharmacokinetics; D005260:Female; D018796:Immunoconjugates / Q000737:chemistry; D007202:Indicators and Reagents; D017879:Isothiocyanates / Q000138:chemical synthesis*; D051379:Mice; D008819:Mice, Nude; D004369:Pentetic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: C434765:2-(p-isothiocyanatobenzyl)-1,4,7,10,13-pentaazacyclopentadecane-N,N',N'',N''',N''''-pentaacetic acid; D002614:Chelating Agents; D018796:Immunoconjugates; D007202:Indicators and Reagents; D017879:Isothiocyanates; D019275:Radiopharmaceuticals; D004369:Pentetic Acid; D001729:Bismuth