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Quantifying Tumor Reoxygenation in Irradiated Murine Breast Tumors in Vivo Using Dual-Emissive Boron Nanoparticles

L Chan1*, H Zhang2 , C DeRosa3 , C Fraser3 , G Palmer2 , (1) Duke Kunshan University, Suzhou, Jiangsu, (2) Duke University, Durham, NC, (3) University of Virginia, Charlottesville, VA

Presentations


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(Sunday, 7/14/2019) 4:00 PM - 4:30 PM

Room: Exhibit Hall | Forum 4

Purpose: To validate the use of dual-emissive boron nanoparticles in quantifying pO₂ of irradiated murine tumors in vivo, and in elucidating reoxygenation kinetics when combined with hyperspectral imaging of hemoglobin saturation

Methods: The fabricated dual-emissive boron nanoparticles featured stable oxygen-independent fluorescence (F) and oxygen-dependent phosphorescence (P). Female C57/BL6 mice were implanted with E0771 tumors in dorsal window chambers. Tumors were grown for 5-10 days and the mice were randomized into two groups – one group was irradiated with 12Gy in an animal irradiator, while the other was sham-irradiated. Hemoglobin saturation and tumor pO₂ measurements were obtained using hyperspectral imaging and fluorescence imaging of injected dual-emissive boron nanoparticles 1 day pre-treatment and 48 hours post-treatment. Fluorescence-to-phosphorescence (F/P) ratios were calculated from fluorescence images of both timepoints as a proxy for tumor pO₂; hemoglobin saturation from both timepoints were calculated using Shonat et al.’s model. 2-way ANOVA statistical tests were used to determine statistical significance in differences between the two timepoints. Pearson’s r testing was conducted to determine correlation between changes in F/P ratio and that of hemoglobin saturation.

Results: Modest increases in F/P ratio that proved significant (p<0.05) were observed after irradiation, but no significance was observed for change in hemoglobin saturation for irradiated mice despite a general increasing trend. No significant changes were observed in sham-irradiated mice. In individual tumors, the direction of the changes in F/P and hemoglobin saturation were usually the same, but the extent of the changes was weakly correlated (r=0.5324).

Conclusion: Reoxygenation 48 hours post-irradiation has been demonstrated in E0771 tumors. Incongruencies between hemoglobin saturation, which measures vascular oxygenation, and F/P ratio, a direct measurement of tumor pO2, suggest that effects of radiation on oxygen supply and demand may differ, thus underscoring the importance of using direct methods to quantify tumor pO₂ in future hypoxia studies.

Keywords

Tumor Vasculature, Hypoxia, Optical Imaging

Taxonomy

TH- Radiobiology(RBio)/Biology(Bio): Bio- tissue and microenvironment

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