Effect of Emulsion Concentration on Biodistribution of Perflubron in Tumor-bearing Mice

Long, David M.; Witt, Brenda L.; Escobar, Juliana; Long, Raymond A.

doi:10.3109/10731199209119739

Cited by 1 publication

(1 citation statement)

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“…Later, second-generation PFC agents were developed towards improved stability and ease of use. For example, Oxygent, a lipid-stabilized perfluorooctyl bromide (CF 3 (CF 2 ) 7 Br, PFOB) nanoemulsion, similarly demonstrated tumor radiosensitization in preclinical tumor models 2,40,41 that was presumed to be due to increased oxygenation in the tumor 42,43. These results were attributed to the increased oxygen-carrying capacity of the PFCs in the bloodstream when applied with enhanced oxygen breathing (i.e., carbogen or HBO).…”

Section: Introductionmentioning

confidence: 99%

Perfluorocarbon nanodroplets can reoxygenate hypoxic tumors in vivo without carbogen breathing

Yun¹,

Bernards²,

Hoang³

et al. 2019

Nanotheranostics

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Nanoscale perfluorocarbon (PFC) droplets have enormous potential as clinical theranostic agents. They are biocompatible and are currently used in vivo as contrast agents for a variety of medical imaging modalities, including ultrasound, computed tomography, photoacoustic and 19 F-magnetic resonance imaging. PFC nanodroplets can also carry molecular and nanoparticulate drugs and be activated in situ by ultrasound or light for targeted therapy. Recently, there has been renewed interest in using PFC nanodroplets for hypoxic tumor reoxygenation towards radiosensitization based on the high oxygen solubility of PFCs. Previous studies showed that tumor oxygenation using PFC agents only occurs in combination with enhanced oxygen breathing. However, recent studies suggest that PFC agents that accumulate in solid tumors can contribute to radiosensitization, presumably due to tumor reoxygenation without enhanced oxygen breathing. In this study, we quantify the impact of oxygenation due to PFC nanodroplet accumulation in tumors alone in comparison with other reoxygenation methodologies, in particular, carbogen breathing. Methods: Lipid-stabilized, PFC (i.e., perfluorooctyl bromide, CF 3 (CF 2 ) 7 Br, PFOB) nanoscale droplets were synthesized and evaluated in xenograft prostate (DU145) tumors in male mice. Biodistribution assessment of the nanodroplets was achieved using a fluorescent lipophilic indocarbocyanine dye label (i.e., DiI dye) on the lipid shell in combination with fluorescence imaging in mice (n≥3 per group). Hypoxia reduction in tumors was measured using PET imaging and a known hypoxia radiotracer, [ 18 F]FAZA (n≥ 3 per group). Results: Lipid-stabilized nanoscale PFOB emulsions (mean diameter of ~250 nm), accumulated in the xenograft prostate tumors in mice 24 hours post-injection. In vivo PET imaging with [ 18 F]FAZA showed that the accumulation of the PFOB nanodroplets in the tumor tissues alone significantly reduced tumor hypoxia, without enhanced oxygen (i.e., carbogen) breathing. This reoxygenation effect was found to be comparable with carbogen breathing alone. Conclusion: Accumulation of nanoscale PFOB agents in solid tumors alone successfully reoxygenated hypoxic tumors to levels comparable with carbogen breathing alone, an established tumor oxygenation method. This study confirms that PFC agents can be used to reoxygenate hypoxic tumors in addition to their current applications as multifunctional theranostic agents.

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