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Nat Commun. 2020 Jan 29;11(1):573. doi: 10.1038/s41467-020-14415-9.

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

Author information

1
Thayer School of Engineering, Dartmouth College, Hanover, NH, USA.
2
Engineering Research Center of Molecular and Neuro Imaging of Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, China.
3
Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
4
Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA.
5
Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
6
Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Biomedical Analytical Technology and Instrumentation, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
7
Department of Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA.
8
CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
9
Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. vinograd.upenn@gmail.com.
10
Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA. vinograd.upenn@gmail.com.
11
Thayer School of Engineering, Dartmouth College, Hanover, NH, USA. brian.w.pogue@dartmouth.edu.
12
Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA. brian.w.pogue@dartmouth.edu.

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.

PMID:
31996677
PMCID:
PMC6989492
DOI:
10.1038/s41467-020-14415-9
[Indexed for MEDLINE]
Free PMC Article

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