論文

査読有り
2013年4月

Evaluation of Zr-89-Labeled Human Anti-CD147 Monoclonal Antibody as a Positron Emission Tomography Probe in a Mouse Model of Pancreatic Cancer

PLOS ONE
  • Aya Sugyo
  • ,
  • Atsushi B. Tsuji
  • ,
  • Hitomi Sudo
  • ,
  • Kotaro Nagatsu
  • ,
  • Mitsuru Koizumi
  • ,
  • Yoshinori Ukai
  • ,
  • Gene Kurosawa
  • ,
  • Ming-Rong Zhang
  • ,
  • Yoshikazu Kurosawa
  • ,
  • Tsuneo Saga

8
4
開始ページ
e61230
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1371/journal.pone.0061230
出版者・発行元
PUBLIC LIBRARY SCIENCE

Introduction: 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 I-125-, Ga-67-, or Zr-89-labeled 059-053. In vivo biodistribution of I-125- or Zr-89-labeled 059-053 was conducted in mice bearing MIA Paca-2 and A4 tumors. PET imaging with [Zr-89]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. [Zr-89]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 [I-125]059-053 uptake was relatively low and decreased with time, suggesting that 059-053 was internalized into tumor cells in vivo and I-125 was released from the cells. PET with [Zr-89]059-053 clearly visualized subcutaneous and orthotopic tumors.
Conclusion: [Zr-89]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.

リンク情報
DOI
https://doi.org/10.1371/journal.pone.0061230
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000319109800132&DestApp=WOS_CPL
ID情報
  • DOI : 10.1371/journal.pone.0061230
  • ISSN : 1932-6203
  • Web of Science ID : WOS:000319109800132

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