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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

(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 pOâ‚‚ 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 pOâ‚‚ in future hypoxia studies.

Keywords

Tumor Vasculature, Hypoxia, Optical Imaging

Taxonomy

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

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