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.

Overcoming tumor hypoxia as a barrier to radiotherapy, chemotherapy and immunotherapy in cancer treatment

“…Compared to carbogen alone, NVX-108 + carbogen resulted in a 400% increase in tumor oxygen levels. 68 Note that results from a preclinical study in a different tumor model analyzing the effects of TSC only saw an increased tumor pO 2 of 40%. 69 In another study of DDFPe (identical material to NVX-108 but without a physiological buffer), administration with carbogen completely reversed radiation resistance in rats with Morris hepatoma.…”

Liposome encapsulated perfluorohexane enhances radiotherapy in mice without additional oxygen supply

“…Usually, PFCs were delivered shortly before radiation (e.g. 1 h) and intended to increase the oxygen content in circulation and thus enhance radiotherapy in the most reported studies [ 9 , 11 , 14 , 24 , 25 ]. Despite the effect of perfluorochemical emulsions on radiosensitization, the efficacy of perfluorochemical emulsions seemed to be very limited since oxygen breathing (95 % O 2 or 100 % O 2 ) before and during the radiotherapy was indispensable.…”

“…Therefore, PFCs were delivered shortly before radiation (e.g. 1 h) and intended to increase the oxygen content in circulation and thus enhance radiotherapy in the most reported studies [ 9 , 11 , 14 , 24 , 25 ].…”

Dynamic oxygenation measurements using a phosphorescent coating within a mammary window chamber mouse model

“…In another set of experiments, an intravenous injection of 0.6 mL/kg body weight NVX-108 (NuvOx Pharma, Tucson, AZ) was administered. NVX-108 is an investigational therapeutic composed of a nano-emulsion of 2% w/vol dodecofluoropentane that binds significant oxygen and increases delivery of oxygen to tissue [12].…”

“…NVX-108 is one such drug under development for increasing oxygenation of hypoxic tumors prior to radiation treatment. The drug has completed preliminary testing in a pancreatic xenograft model, and has moved onto a clinical trials in the context of treating gliomas [12]. The drug has potential for expanding into other common hypoxic tumor types, including breast cancers.…”