Co-imaging of the tumor oxygenation and metabolism using electron paramagnetic resonance imaging and 13-C hyperpolarized magnetic resonance imaging before and after irradiation

Masayuki Matsuo; Tatsuya Kawai; Shun Kishimoto; Keita Saito; Jeeva Munasinghe; Nallathamby Devasahayam; James B. Mitchell; Murali C. Krishna

doi:10.18632/oncotarget.25317

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Research Papers:

Co-imaging of the tumor oxygenation and metabolism using electron paramagnetic resonance imaging and 13-C hyperpolarized magnetic resonance imaging before and after irradiation

Masayuki Matsuo, Tatsuya Kawai, Shun Kishimoto, Keita Saito, Jeeva Munasinghe, Nallathamby Devasahayam, James B. Mitchell and Murali C. Krishna _

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Oncotarget. 2018; 9:25089-25100. https://doi.org/10.18632/oncotarget.25317

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Abstract

Masayuki Matsuo1,4, Tatsuya Kawai2, Shun Kishimoto1, Keita Saito1, Jeeva Munasinghe3, Nallathamby Devasahayam1, James B. Mitchell1 and Murali C. Krishna1

1Radiation Biology Branch, Center for Cancer research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

2Radiation Oncology Branch, Center for Cancer research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

3MRI Research Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA

4Department of Radiology, Gifu University Graduate School of Medicine, Gifu City, Japan

Correspondence to:

Murali C. Krishna, email: [email protected]

Keywords: pO₂; ESR imaging; 1-13C MRI; glycolytic metabolism; radiation therapy

Received: November 08, 2017 Accepted: April 02, 2018 Published: May 18, 2018

ABSTRACT

To examine the relationship between local oxygen partial pressure and energy metabolism in the tumor, electron paramagnetic resonance imaging (EPRI) and magnetic resonance imaging (MRI) with hyperpolarized [1-¹³C] pyruvate were performed.

SCCVII and HT29 solid tumors implanted in the mouse leg were imaged by EPRI using OX063, a paramagnetic probe and ¹³C-MRI using hyperpolarized [1-¹³C] pyruvate. Local partial oxygen pressure and pyruvate metabolism in the two tumor implants were examined. The effect of a single dose of 5-Gy irradiation on the pO₂ and metabolism was also investigated by sequential imaging of EPRI and ¹³C-MRI in HT29 tumors.

A phantom study using tubes filled with different concentration of [1-¹³C] pyruvate, [1-¹³C] lactate, and OX063 at different levels of oxygen confirmed the validity of this sequential imaging of EPRI and hyperpolarized ¹³C-MRI. In vivo studies revealed SCCVII tumor had a significantly larger hypoxic fraction (pO₂ < 8 mmHg) compared to HT29 tumor. The flux of pyruvate-to-lactate conversion was also higher in SCCVII than HT29. The lactate-to-pyruvate ratio in hypoxic regions (pO₂ < 8 mmHg) 24 hours after 5-Gy irradiation was significantly higher than those without irradiation (0.76 vs. 0.36) in HT29 tumor. The in vitro study showed an increase in extracellular acidification rate after irradiation.

In conclusion, co-imaging of pO₂ and pyruvate-to-lactate conversion kinetics successfully showed the local metabolic changes especially in hypoxic area induced by radiation therapy.

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Research Papers:

Co-imaging of the tumor oxygenation and metabolism using electron paramagnetic resonance imaging and 13-C hyperpolarized magnetic resonance imaging before and after irradiation

Abstract