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Evaluating Tumor Hypoxia Radiosensitization Via Electron Paramagnetic Resonance Oxygen Imaging (EPROI).

Publication ,  Journal Article
Rickard, AG; Mowery, YM; Bassil, A; Rouse, DC; Williams, NT; Charity, T; Belloni, R; Crouch, B; Ramanujam, N; Stevenson, D; Castillo, R ...
Published in: Mol Imaging Biol
September 18, 2023

PURPOSE: Tumor hypoxia contributes to aggressive phenotypes and diminished therapeutic responses to radiation therapy (RT) with hypoxic tissue being 3-fold less radiosensitive than normoxic tissue. A major challenge in implementing hypoxic radiosensitizers is the lack of a high-resolution imaging modality that directly quantifies tissue-oxygen. The electron paramagnetic resonance oxygen-imager (EPROI) was used to quantify tumor oxygenation in two murine tumor models: E0771 syngeneic transplant breast cancers and primary p53/MCA soft tissue sarcomas, with the latter autochthonous model better recapitulating the tumor microenvironment in human malignancies. We hypothesized that tumor hypoxia differs between these models. We also aimed to quantify the absolute change in tumor hypoxia induced by the mitochondrial inhibitor papaverine (PPV) and its effect on RT response. PROCEDURES: Tumor oxygenation was characterized in E0771 and primary p53/MCA sarcomas via EPROI, with the former model also being quantified indirectly via diffuse reflectance spectroscopy (DRS). After confirming PPV's effect on hypoxic fraction (via EPROI), we compared the effect of 0 versus 2 mg/kg PPV prior to 20 Gy on tumor growth delay and survival. RESULTS: Hypoxic sarcomas were more radioresistant than normoxic sarcomas (p=0.0057, 2-way ANOVA), and high baseline hypoxic fraction was a significant (p=0.0063, Cox Regression Model) hazard in survivability regardless of treatment. Pre-treatment with PPV before RT did not radiosensitize tumors in the sarcoma or E0771 model. In the sarcoma model, EPROI successfully identified baseline hypoxic tumors. DRS quantification of total hemoglobin, saturated hemoglobin, changes in mitochondrial potential and glucose uptake showed no significant difference in E0771 tumors pre- and post-PPV. CONCLUSION: EPROI provides 3D high-resolution pO2 quantification; EPR is better suited than DRS to characterize tumor hypoxia. PPV did not radiosensitize E0771 tumors nor p53/MCA sarcomas, which may be related to the complex pattern of vasculature in each tumor. Additionally, understanding model-dependent tumor hypoxia will provide a much-needed foundation for future therapeutic studies with hypoxic radiosensitizers.

Duke Scholars

Published In

Mol Imaging Biol

DOI

EISSN

1860-2002

Publication Date

September 18, 2023

Location

United States

Related Subject Headings

  • Nuclear Medicine & Medical Imaging
  • 3202 Clinical sciences
  • 1103 Clinical Sciences
  • 0606 Physiology
 

Citation

APA
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MLA
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Rickard, A. G., Mowery, Y. M., Bassil, A., Rouse, D. C., Williams, N. T., Charity, T., … Palmer, G. M. (2023). Evaluating Tumor Hypoxia Radiosensitization Via Electron Paramagnetic Resonance Oxygen Imaging (EPROI). Mol Imaging Biol. https://doi.org/10.1007/s11307-023-01855-0
Rickard, Ashlyn G., Yvonne M. Mowery, Alex Bassil, Douglas C. Rouse, Nerissa T. Williams, Theresa Charity, Rafaela Belloni, et al. “Evaluating Tumor Hypoxia Radiosensitization Via Electron Paramagnetic Resonance Oxygen Imaging (EPROI).Mol Imaging Biol, September 18, 2023. https://doi.org/10.1007/s11307-023-01855-0.
Rickard AG, Mowery YM, Bassil A, Rouse DC, Williams NT, Charity T, et al. Evaluating Tumor Hypoxia Radiosensitization Via Electron Paramagnetic Resonance Oxygen Imaging (EPROI). Mol Imaging Biol. 2023 Sep 18;
Rickard, Ashlyn G., et al. “Evaluating Tumor Hypoxia Radiosensitization Via Electron Paramagnetic Resonance Oxygen Imaging (EPROI).Mol Imaging Biol, Sept. 2023. Pubmed, doi:10.1007/s11307-023-01855-0.
Rickard AG, Mowery YM, Bassil A, Rouse DC, Williams NT, Charity T, Belloni R, Crouch B, Ramanujam N, Stevenson D, Castillo R, Blocker S, Epel B, Kotecha M, Palmer GM. Evaluating Tumor Hypoxia Radiosensitization Via Electron Paramagnetic Resonance Oxygen Imaging (EPROI). Mol Imaging Biol. 2023 Sep 18;
Journal cover image

Published In

Mol Imaging Biol

DOI

EISSN

1860-2002

Publication Date

September 18, 2023

Location

United States

Related Subject Headings

  • Nuclear Medicine & Medical Imaging
  • 3202 Clinical sciences
  • 1103 Clinical Sciences
  • 0606 Physiology