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Radiosensitization of Hs-766T Pancreatic Tumor Xenografts in Mice Dosed with Dodecafluoropentane Nano-Emulsion-Preliminary Findings.

Abstract
Tumor hypoxia is an important mediator of radiation therapy resistance. We conducted a study to investigate whether an oxygen therapeutic based upon dodecafluoropentane (DDFP) nano-emulsion (NVX-108) could increase tumor PO2 in hypoxic tumors and improve radiation response. Pancreatic (Hs-766T) tumor xenografts were grown in the flanks of 29 SCID mice. Direct tumor PO2 measurements were performed in 9 mice treated with 0.3, 0.45 and 0.6 cc/kg NVX-108 (2% w/vol DDFP) in order to assess the dose dependent increase in tumor PO2. Twenty mice were randomized into 3 groups including control (no treatment), carbogen breathing treated with 12 Gy radiation, and carbogen breathing treated with 12 Gy radiation and NVX-108 (0.6 cc/kg NVX-108 administered as 30 minute IV infusion at time of radiation). Tumor volume was monitored to assess treatment efficacy. Results showed that tumor PO2 increased in NVX-108 treated mice up to 400% with the greatest effect seen at the highest dose of 0.6 cc/kg. Tumor growth was significantly reduced in both treatment groups relative to controls (p < 0.0001). The combination of carbogen, radiation, and NVX-108 demonstrated a 2-fold reduction in average tumor volume compared to carbogen plus radiation treatment (p = 0.01). Further study of NVX-108 as a radiation sensitizer is warranted.
AuthorsJennifer L H Johnson, Rafael A Leos, Amanda F Baker, Evan C Unger
JournalJournal of biomedical nanotechnology (J Biomed Nanotechnol) Vol. 11 Issue 2 Pg. 274-81 (Feb 2015) ISSN: 1550-7033 [Print] United States
PMID26349303 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Emulsions
  • Fluorocarbons
  • Radiation-Sensitizing Agents
  • perfluoropentane
Topics
  • Animals
  • Cell Hypoxia (drug effects)
  • Cell Line, Tumor
  • Emulsions
  • Female
  • Fluorocarbons (administration & dosage, pharmacokinetics)
  • Humans
  • Mice
  • Mice, SCID
  • Nanoparticles (administration & dosage)
  • Pancreatic Neoplasms (drug therapy, metabolism, radiotherapy)
  • Pilot Projects
  • Radiation Tolerance (drug effects)
  • Radiation-Sensitizing Agents (administration & dosage, pharmacokinetics)
  • Xenograft Model Antitumor Assays

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