title: Epidermal growth factor receptor-targeted radioimmunotherapy of human head and neck cancer xenografts using 90Y-labeled fully human antibody panitumumab.
abstract: Panitumumab (ABX-EGF or Vectibix), the first fully human monoclonal antibody targeting epidermal growth factor receptor (EGFR), was approved by the Food and Drug Administration for treatment of patients with metastatic colorectal cancer. Here, we report for the first time the radioimmunotherapy (RIT) of EGFR-positive human head and neck cancer in a nude mouse model using pure beta(-) emitter (90)Y-labeled panitumumab. Biodistribution and planar gamma-imaging studies were carried out with (111)In-DOTA-panitumumab. The RIT efficacy of (90)Y-DOTA-panitumumab was evaluated in UM-SCC-22B tumor model. CD31, Ki67, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and H&E staining were done on UM-SCC-22B tumor sections after treatment. The tumor uptake of (111)In-DOTA-panitumumab in UM-SCC-22B tumor-bearing nude mice was 26.10 +/- 4.93, 59.11 +/- 7.22, 44.57 +/- 9.80, 40.38 +/- 7.76, and 14.86 +/- 7.23 % injected dose per gram of tissue at 4, 24, 72, 120, and 168 hours after injection, respectively. Immunotherapy with cold panitumumab (four doses of 10 mg/kg) did not cause significant antitumor effect. RIT with a single dose of 100 microCi (90)Y-DOTA-panitumumab caused significant tumor growth delay and improved the survival in UM-SCC-22B tumor model. A single dose of 200 microCi (90)Y-DOTA-panitumumab led to almost complete tumor regression (tumor volumes were 34.83 +/- 11.11 mm(3) and 56.02 +/- 39.95 mm(3) on days 0 and 46 after treatment, respectively). Histopathologic analysis of tumors and normal organs further validated the therapeutic efficacy and limited systemic toxicity of (90)Y-DOTA-panitumumab. The high tumor uptake and prolonged tumor retention, as well as effective therapy, reveal that (90)Y-DOTA-panitumumab may be a promising radioimmunotherapeutic agent to treat EGFR-positive solid tumors.
authors.affiliation: Medical Isotopes Research Center, Peking University, 38 Xueyuan Road, Beijing 100191, China.
authors.forename: Zhaofei
authors.initials: Z
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Bing
authors.initials: B
authors.lastname: Jia
authors.forename: Huiyun
authors.initials: H
authors.lastname: Zhao
authors.forename: Xiaona
authors.initials: X
authors.lastname: Jin
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D015902:Gamma Cameras; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D051379:Mice; D009942:Organometallic Compounds / Q000494:pharmacology / Q000627:therapeutic use; D000077544:Panitumumab; D016499:Radioimmunotherapy / Q000379:methods*; D014018:Tissue Distribution / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D015021:Yttrium Radioisotopes
chemical_list: D000911:Antibodies, Monoclonal; D009942:Organometallic Compounds; D015021:Yttrium Radioisotopes; D000077544:Panitumumab; D066246:ErbB Receptors