Cancer Chemotherapy and Pharmacology

, Volume 66, Issue 4, pp 745–753 | Cite as

Biodistribution of humanized anti-VEGF monoclonal antibody/bevacizumab on peritoneal metastatic models with subcutaneous xenograft of gastric cancer in mice

  • Yasumichi Yagi
  • Sachio Fushida
  • Shinichi Harada
  • Tomoya Tsukada
  • Jun Kinoshita
  • Katsunobu Oyama
  • Hideto Fujita
  • Itasu Ninomiya
  • Takashi Fujimura
  • Masato Kayahara
  • Seigo Kinuya
  • Masakazu Yashiro
  • Kousei Hirakawa
  • Tetsuo Ohta
Original Article

Abstract

Purpose

Vascular endothelial growth factor (VEGF) is correlated with peritoneal metastasis of gastric cancer, increasing vascular permeability accompanied by accumulation of ascites. The aim of the current study is to investigate the biodistribution of bevacizumab in a peritoneal metastatic model of gastric cancer and to clarify which is more suited to treatment of peritoneal metastasis, systemic or regional therapy.

Methods

A highly peritoneal-seeding cell line of gastric cancer, OCUM-2MD3, which exhibited high production and release of VEGF was used in this study. The biodistribution of bevacizumab was investigated using peritoneal metastatic models together with subcutaneous xenografts, and 125I-radiolabelled bevacizumab was administrated to these models subcutaneously (s.c.) or intraperitoneally (i.p.), respectively. In addition, the anti-tumor response of bevacizumab and paclitaxel was assessed as single agents or in combination using peritoneal metastatic models.

Results

In the analysis of biodistribution, 125I-bevacizumab administrated i.p. indicated low peritoneal clearance. On the other hand, s.c. administration of 125I-bevacizumab showed preferential accumulation in subcutaneous tumors and peritoneal nodules, with a high blood concentration. In peritoneal metastatic models, the effects of bevacizumab were found for both the growth inhibition of peritoneal nodules (P < 0.01) and the reduction of ascites (P < 0.05). These effects were more prominent by s.c. administration compared with i.p. administration and were increased in combination with i.p. paclitaxel.

Conclusion

Bevacizumab should be administrated systemically compared to regionally, and the combination with i.p. paclitaxel has a potential to be useful for patients with peritoneal metastasis of gastric cancer.

Keywords

Peritoneal metastasis Bevacizumab Biodistribution Iodine-125 label Molecular-targeted therapy 

Notes

Acknowledgments

The authors declare that there are no conflicts of interest and no support in this study.

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Yasumichi Yagi
    • 1
  • Sachio Fushida
    • 1
  • Shinichi Harada
    • 2
  • Tomoya Tsukada
    • 1
  • Jun Kinoshita
    • 1
  • Katsunobu Oyama
    • 1
  • Hideto Fujita
    • 1
  • Itasu Ninomiya
    • 1
  • Takashi Fujimura
    • 1
  • Masato Kayahara
    • 1
  • Seigo Kinuya
    • 3
  • Masakazu Yashiro
    • 4
  • Kousei Hirakawa
    • 4
  • Tetsuo Ohta
    • 1
  1. 1.Department of Gastroenterologic Surgery, Division of Cancer Medicine, Graduate School of Medical ScienceKanazawa UniversityKanazawa, IshikawaJapan
  2. 2.Center for Biomedical Research and Education, School of MedicineKanazawa UniversityIshikawaJapan
  3. 3.Department of Biotracer Medicine, Graduate School of Medical ScienceKanazawa UniversityIshikawaJapan
  4. 4.Department of Surgical Oncology, Graduate School of MedicineOsaka City UniversityOsakaJapan

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