Dataset Information

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

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.

SUBMITTER: Cao X

PROVIDER: S-EPMC6989492 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Tissue pO<sub>2</sub> distributions in xenograft tumors dynamically imaged by Cherenkov-excited phosphorescence during fractionated radiation therapy.

Cao Xu X Rao Allu Srinivasa S Jiang Shudong S Jia Mengyu M Gunn Jason R JR Yao Cuiping C LaRochelle Ethan P EP Shell Jennifer R JR Bruza Petr P Gladstone David J DJ Jarvis Lesley A LA Tian Jie J Vinogradov Sergei A SA Pogue Brian W BW

Nature communications 20200129 1

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 (pO<sub>2</sub>) 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 ph ...[more]

PMID: 31996677

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Project description:BackgroundMechanical ventilation can lead to ventilator-induced lung injury (VILI). In addition to the well-known mechanical forces of volutrauma, barotrauma, and atelectrauma, non-mechanical mechanisms have recently been discussed as contributing to the pathogenesis of VILI. One such mechanism is oscillations in partial pressure of oxygen (PO2) which originate in lung tissue in the presence of within-breath recruitment and derecruitment of alveoli. The purpose of this study was to investigate this mechanism's possible independent effects on lung tissue and inflammation in a porcine model.MethodsTo separately study the impact of PO2 oscillations on the lungs, an in vivo model was set up that allowed for generating mixed-venous PO2 oscillations by the use of veno-venous extracorporeal membrane oxygenation (vvECMO) in a state of minimal mechanical stress. While applying the identical minimal-invasive ventilator settings, 16 healthy female piglets (weight 50 ± 4 kg) were either exposed for 6 h to a constant mixed-venous hemoglobin saturation (SmvO2) of 65% (which equals a PmvO2 of 41 Torr) (control group), or an oscillating SmvO2 (intervention group) of 40-90% (which equals PmvO2 oscillations of 30-68 Torr)-while systemic normoxia in both groups was maintained. The primary endpoint of histologic lung damage was assessed by ex vivo histologic lung injury scoring (LIS), the secondary endpoint of pulmonary inflammation by qRT-PCR of lung tissue. Cytokine concentration of plasma was carried out by ELISA. A bioinformatic microarray analysis of lung samples was performed to generate hypotheses about underlying pathomechanisms.ResultsThe LIS showed significantly more severe damage of lung tissue after exposure to PO2 oscillations compared to controls (0.53 [0.51; 0.58] vs. 0.27 [0.23; 0.28]; P = 0.0025). Likewise, a higher expression of TNF-α (P = 0.0127), IL-1β (P = 0.0013), IL-6 (P = 0.0007), and iNOS (P = 0.0013) in lung tissue was determined after exposure to PO2 oscillations. Cytokines in plasma showed a similar trend between the groups, however, without significant differences. Results of the microarray analysis suggest that inflammatory (IL-6) and oxidative stress (NO/ROS) signaling pathways are involved in the pathology linked to PO2 oscillations.ConclusionsArtificial mixed-venous PO2 oscillations induced lung damage and pulmonary inflammation in healthy animals during lung protective ventilation. These findings suggest that PO2 oscillations represent an independent mechanism of VILI.

Dataset Information

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

Publications

Tissue pO<sub>2</sub> distributions in xenograft tumors dynamically imaged by Cherenkov-excited phosphorescence during fractionated radiation therapy.

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Dataset Information

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

Publications

Tissue pO<sub>2</sub> distributions in xenograft tumors dynamically imaged by Cherenkov-excited phosphorescence during fractionated radiation therapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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