title: Evaluation of (89)Zr-labeled human anti-CD147 monoclonal antibody as a positron emission tomography probe in a mouse model of pancreatic cancer.
abstract: BACKGROUND
  Pancreatic cancer is an aggressive cancer and its prognosis remains poor. Therefore, additional effective therapy is required to augment and/or complement current therapy. CD147, high expression in pancreatic cancer, is involved in the metastatic process and is considered a good candidate for targeted therapy. CD147-specfic imaging could be useful for selection of appropriate patients. Therefore, we evaluated the potential of a fully human anti-CD147 monoclonal antibody 059-053 as a new positron emission tomography (PET) probe for pancreatic cancer.
  
  
  METHODS
  CD147 expression was evaluated in four pancreatic cancer cell lines (MIA Paca-2, PANC-1, BxPC-3, and AsPC-1) and a mouse cell line A4 as a negative control. Cell binding, competitive inhibition and internalization assays were conducted with (125)I-, (67)Ga-, or (89)Zr-labeled 059-053. In vivo biodistribution of (125)I- or (89)Zr-labeled 059-053 was conducted in mice bearing MIA Paca-2 and A4 tumors. PET imaging with [(89)Zr]059-053 was conducted in subcutaneous and orthotopic tumor mouse models.
  
  
  RESULTS
  Among four pancreatic cancer cell lines, MIA Paca-2 cells showed the highest expression of CD147, while A4 cells had no expression. Immunohistochemical staining showed that MIA Paca-2 xenografts also highly expressed CD147 in vivo. Radiolabeled 059-053 specifically bound to MIA Paca-2 cells with high affinity, but not to A4. [(89)Zr]059-053 uptake in MIA Paca-2 tumors increased with time from 11.0±1.3% injected dose per gram (ID/g) at day 1 to 16.9±3.2% ID/g at day 6, while [(125)I]059-053 uptake was relatively low and decreased with time, suggesting that 059-053 was internalized into tumor cells in vivo and (125)I was released from the cells. PET with [(89)Zr]059-053 clearly visualized subcutaneous and orthotopic tumors.
  
  
  CONCLUSIONS
  [(89)Zr]059-053 is a promising PET probe for imaging CD147 expression in pancreatic cancer and has the potential to select appropriate patients with CD147-expressing tumors who could gain benefit from anti-CD147 therapy.
authors.affiliation: Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Sugyo
authors.forename: Atsushi B
authors.initials: AB
authors.lastname: Tsuji
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sudo
authors.forename: Kotaro
authors.initials: K
authors.lastname: Nagatsu
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Koizumi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ukai
authors.forename: Gene
authors.initials: G
authors.lastname: Kurosawa
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
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 / Q000276:immunology / Q000493:pharmacokinetics; D051926:Basigin / Q000276:immunology*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D049268:Positron-Emission Tomography / Q000379:methods*; D011868:Radioisotopes; D015040:Zirconium
chemical_list: D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D051926:Basigin; D015040:Zirconium