title: Novel human monoclonal antibody against epidermal growth factor receptor as an imaging probe for hepatocellular carcinoma.
abstract: OBJECTIVE
  The epidermal growth factor receptor (EGFR) is overexpressed in many epithelial cancers, including hepatocellular carcinoma (HCC), and is an attractive target for cancer imaging and therapy. We attempted a novel noninvasive imaging method to evaluate anti-EGFR human monoclonal antibody clones for determining the uptake of therapeutic anti-EGFR antibody in HCC.
  
  
  METHODS
  In-vitro cell binding of nine I-labeled antibody clones was compared in the human epidermoid cancer cell line A431, in three HCC cell lines Hep-G2, SK-Hep1, and HuH-7, and in the EGFR-negative control cell line A4. In-labeled or I-labeled 048-006 was subjected to cell binding, competitive inhibition, and internalization assays using A431, SK-Hep1, and HuH-7. Further, In-labeled 048-006 was evaluated in in-vivo biodistribution analysis and single-photon imaging in nude tumor-bearing mice.
  
  
  RESULTS
  The 048-006 clone showed the highest binding to EGFR-expressing cells among the nine antibodies. In-labeled or I-labeled 048-006 specifically bound to EGFR-expressing cells with high affinity and was internalized after binding to EGFR. A431 and HuH-7 tumors showed high In-labeled 048-006 uptake, which was visualized by single-photon imaging.
  
  
  CONCLUSIONS
  Radiolabeled human anti-EGFR monoclonal antibody 048-006 has the potential to be a safer imaging probe for predicting tumor uptake of anti-EGFR antibody therapeutic agents in HCC.
authors.affiliation: Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Chizuru
authors.initials: C
authors.lastname: Sogawa
authors.forename: Atsushi B
authors.initials: AB
authors.lastname: Tsuji
authors.forename: Chisato
authors.initials: C
authors.lastname: Yoshida
authors.forename: Masayuki
authors.initials: M
authors.lastname: Inubushi
authors.forename: Takako
authors.initials: T
authors.lastname: Furukawa
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Koizumi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Akahori
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ukai
authors.forename: Gene
authors.initials: G
authors.lastname: Kurosawa
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kurosawa
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Saga
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000378:metabolism; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008114:Liver Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D066246:ErbB Receptors