Systemic Administration of Hemoglobin Vesicle Elevates Tumor Tissue Oxygen Tension and Modifies Tumor Response to Irradiation

Manabu Yamamoto, Yotaro Izumi, Hirohisa Horinouchi, Yuji Teramura, Hiromi Sakai, Mitsutomo Kohno, Masazumi Watanabe, Masafumi Kawamura, Takeshi Adachi, Eiji Ikeda, Shinji Takeoka, Eishun Tsuchida, Koichi Kobayashi

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12 Citations (Scopus)

Abstract

Background: We have developed a phospholipid liposome vesicle encapsulating concentrated human hemoglobin (hemoglobin vesicle, HbV) as an artificial oxygen carrier, as an alternative to red cell transfusion. We have verified its oxygen transporting capability in a variety of preclinical models. Recent evidence suggests that artificial oxygen carriers may also be applicable for better oxygenation of ischemic or hypoxic tissues including tumors. To our knowledge, tumor oxygenation using a liposome-type artificial oxygen carrier has not been closely tested. In the present study, we tested whether systemic HbV administration changes tumor tissue oxygen tension, and if it modifies tumor response to irradiation. Materials and methods: Lewis lung carcinoma was grown subcutaneously in the left hindleg of C57BL/6 mice. Experiments were initiated when the tumors reached approximately 8 mm. All experiments were done under room air. Tumor tissue oxygen tension was measured by phosphorescence quenching up to 45 min after systemic sample administration (saline: n = 5; HbV: n = 5; HbV containing methemoglobin (metHbV): n = 4; HbV with high oxygen affinity (lowP50HbV): n = 8) and compared between samples. To test the effects on irradiation response, samples (saline: n = 7; HbV: n = 7; metHbV: n = 7; lowP50HbV: n = 7) were administered prior to single 20-Gy irradiation, and tumor growth was compared. Results: Tumor tissue oxygen tension transiently increased approximately 2-fold after HbV administration in comparison to other samples. Tumor growth was marginally delayed after irradiation by prior administration of HbV in comparison to other samples. HbV administration without irradiation did not affect significant tumor growth delay. Conclusions: These results correlatively suggest that HbV augmented tumor growth delay following irradiation, at least in part, by affecting tumor tissue oxygen tension.

Original languageEnglish
Pages (from-to)48-54
Number of pages7
JournalJournal of Surgical Research
Volume151
Issue number1
DOIs
Publication statusPublished - 2009 Jan 1

Keywords

  • HIF1alpha
  • artificial oxygen carrier
  • hemoglobin vesicle
  • liposome
  • radiosensitizer
  • tumor oxygenation

ASJC Scopus subject areas

  • Surgery

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    Yamamoto, M., Izumi, Y., Horinouchi, H., Teramura, Y., Sakai, H., Kohno, M., Watanabe, M., Kawamura, M., Adachi, T., Ikeda, E., Takeoka, S., Tsuchida, E., & Kobayashi, K. (2009). Systemic Administration of Hemoglobin Vesicle Elevates Tumor Tissue Oxygen Tension and Modifies Tumor Response to Irradiation. Journal of Surgical Research, 151(1), 48-54. https://doi.org/10.1016/j.jss.2007.12.770