title: Cetuximab: preclinical evaluation of a monoclonal antibody targeting EGFR for radioimmunodiagnostic and radioimmunotherapeutic applications.
abstract: The monoclonal antibody, cetuximab, binds to epidermal growth-factor receptor and thus provides an opportunity to create both imaging and therapies that target this receptor. The potential of cetuximab as a radioimmunoconjugate, using the acyclic bifunctional chelator, CHX-A"-DTPA, was investigated. The pharmacokinetic behavior in the blood was determined in mice with and without tumors. Tumor targeting and scintigraphic imaging were evaluated in mice bearing xenografts of LS-174T (colorectal), SHAW (pancreatic), SKOV3 (ovarian), DU145 (prostate), and HT-29 (colorectal). Excellent tumor targeting was observed in each of the models with peak tumor uptakes of 59.8 +/- 18.1, 22.5 +/- 4.7, 33.3 +/- 5.7, 18.2 +/- 7.8, and 41.7 +/- 10.8 injected dose per gram (%ID/g) at 48-72 hours, respectively. In contrast, the highest tumor %ID/g obtained in mice bearing melanoma (A375) xenografts was 6.3 +/- 1.1 at 72 hours. The biodistribution of (111)In-cetuximab was also evaluated in nontumor-bearing mice. The highest %ID/g was observed in the liver (9.3 +/- 1.3 at 24 hours) and the salivary glands (8.1 +/- 2.8 at 72 hours). Scintigraphy showed excellent tumor targeting at 24 hours. Blood pool was evident, as expected, but cleared over time. At 168 hours, the tumor was clearly discernible with negligible background.
authors.affiliation: Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Diane E
authors.initials: DE
authors.lastname: Milenic
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Wong
authors.forename: Kwamena E
authors.initials: KE
authors.lastname: Baidoo
authors.forename: Geoffrey L
authors.initials: GL
authors.lastname: Ray
authors.forename: Kayhan
authors.initials: K
authors.lastname: Garmestani
authors.forename: Mark
authors.initials: M
authors.lastname: Williams
authors.forename: Martin W
authors.initials: MW
authors.lastname: Brechbiel
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D000068818:Cetuximab; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology*; D007205:Indium Radioisotopes / Q000494:pharmacology; D008545:Melanoma / Q000628:therapy; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy / Q000379:methods*; D012469:Salivary Glands / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018796:Immunoconjugates; D007205:Indium Radioisotopes; D066246:ErbB Receptors; D000068818:Cetuximab