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.