Tissue pO2 distributions in xenograft tumors dynamically imaged by Cherenkov-excited phosphorescence during fractionated radiation therapy

Xu Cao, Srinivasa Rao Allu, Shudong Jiang, Mengyu Jia, Jason R. Gunn, Cuiping Yao, Ethan P. LaRochelle, Jennifer R. Shell, Petr Bruza, David J. Gladstone, Lesley A. Jarvis, Jie Tian, Sergei A. Vinogradov () and Brian W. Pogue ()
Additional contact information
Xu Cao: Dartmouth College
Srinivasa Rao Allu: University of Pennsylvania
Shudong Jiang: Dartmouth College
Mengyu Jia: Dartmouth College
Jason R. Gunn: Dartmouth College
Cuiping Yao: Dartmouth College
Ethan P. LaRochelle: Dartmouth College
Jennifer R. Shell: Dartmouth College
Petr Bruza: Dartmouth College
David J. Gladstone: Dartmouth College
Lesley A. Jarvis: Dartmouth-Hitchcock Medical Center
Jie Tian: Xidian University
Sergei A. Vinogradov: University of Pennsylvania
Brian W. Pogue: Dartmouth College

Nature Communications, 2020, vol. 11, issue 1, 1-9

Abstract: Abstract Hypoxia in solid tumors is thought to be an important factor in resistance to therapy, but the extreme microscopic heterogeneity of the partial pressures of oxygen (pO2) between the capillaries makes it difficult to characterize the scope of this phenomenon without invasive sampling of oxygen distributions throughout the tissue. Here we develop a non-invasive method to track spatial oxygen distributions in tumors during fractionated radiotherapy, using oxygen-dependent quenching of phosphorescence, oxygen probe Oxyphor PtG4 and the radiotherapy-induced Cherenkov light to excite and image the phosphorescence lifetimes within the tissue. Mice bearing MDA-MB-231 breast cancer and FaDu head neck cancer xenografts show different pO2 responses during each of the 5 fractions (5 Gy per fraction), delivered from a clinical linear accelerator. This study demonstrates subsurface in vivo mapping of tumor pO2 distributions with submillimeter spatial resolution, thus providing a methodology to track response of tumors to fractionated radiotherapy.

Date: 2020
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DOI: 10.1038/s41467-020-14415-9

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