title: A novel bifunctional maleimido CHX-A'' chelator for conjugation to thiol-containing biomolecules.
abstract: A novel bifunctional maleimido CHX-A'' DTPA chelator 5 was developed and conjugated to the monoclonal antibody trastuzumab (Herceptin) and subsequently radiolabeled with (111)In. The resulting (111)In labeled immunoconjugate 2 was demonstrated to bind to SKOV-3 ovarian cancer cells comparably to an isothiocyanato CHX-A'' DTPA modified native trastuzumab, 1. Through efficient thiol-maleimide chemistry, antibodies, peptides or other targeting vectors can now be modified with an established radioactive metal chelating agent CHX-A'' DTPA for imaging and/or therapies of cancer.
authors: Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 1B40, 10 Center Drive, Bethesda, MD 20892-1088, USA.
authors: Heng
authors: H
authors: Xu
authors: Kwamena E
authors: KE
authors: Baidoo
authors: Karen J
authors: KJ
authors: Wong
authors: Martin W
authors: MW
authors: Brechbiel
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D017879:Isothiocyanates / Q000138:chemical synthesis / Q000737:chemistry*; D008301:Maleimides / Q000737:chemistry*; D015394:Molecular Structure; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry* / Q000378:metabolism*; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D002614:Chelating Agents; D017879:Isothiocyanates; D008301:Maleimides; D013438:Sulfhydryl Compounds; C085678:N-(2-amino-3-(4-isothiocyanatophenyl)propyl)cyclohexane-1,2-diamine-N,N',N',N'',N''-pentaacetic acid; C043592:maleimide; D004369:Pentetic Acid; D000068878:Trastuzumab