Radiation Biology

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SU_42_2421 - Estimation of Re-Appearance of Cycling Hypoxia after Irradiation

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

Estimation of Re-Appearance of Cycling Hypoxia after Irradiation
M. Matsuo1,2, F. Hyodo2,3, H. Tanaka1, T. Yamaguchi1, M. Krishna2, and J. B. Mitchell4; 1Gifu University, Department of Radiology, Gifu, Japan, 2National Institutes of Health, Bethesda, MD, 3Gifu University, Department of Frontier Science for Imaging, Gifu, Japan, 4National Cancer Institute, National Institutes of Health, Bethesda, MD

Purpose/Objective(s):

pO2 levels are linked to many pathophysiological conditions, and oxygen deficiency increases the tumor’s resistance toward cancer treatment. Malignant tumors represent the higher frequency of the cycling hypoxia that can influence HIF1 transcriptional activity, then, it has become much more important to clearly understand the appearance of the cycling hypoxia in radiation therapy. Pulsed electron paramagnetic resonance imaging (EPRI) is a novel imaging method to directly monitor the pO2 in a tumor on a quantitative basis. The purpose of this work was to assess the cycling hypoxia in radiation therapy using murine models of human cancer.

Materials/Methods:

EPRI is a spectroscopic technique similar to nuclear magnetic resonance. EPRI detects paramagnetic species that have unpaired electrons such as transition metal complexes and free radicals. With the recent availability of triarylmethyl radical probes as in vivo compatible paramagnetic tracers, EPRI is now being explored for mapping tissue oxygen in live animals. Recent developments in instrumentation and image acquisition strategy made it possible to obtain three-dimensional pO2 maps within 3 minutes, enabling noninvasive imaging of cycling hypoxia in tumors. HT29 and HCT 116 solid tumors were formed by injecting 1 × 106 cells s.c. into the right hind legs of nude mice. The experiments were started when tumors grew to approximately 800 mm3. The spatial resolution was 1.8 mm. EPRI was performed before and at 24 hours after 3 Gy irradiation. Mice were fixed in a specially designed jig for X-irradiation, by which mice were restricted to move without anesthesia. X-irradiation was delivered using a XRAD-320.

Results:

Before and 24 hours after 3 Gy irradiation, to visualize dynamic changes of tumor oxygenation over a time period of 30 minutes, EPRI experiments were carried out collecting nine image data sets, each taking 3 minutes, for a three-dimensional reconstruction of pO2 maps as well as the tracer distribution.

Not only before irradiation, but also at 24 hours after 3 Gy irradiation, our results showed when hypoxic levels in the two ROIs (ROI 1 an ROI 2), ROI 1 displayed relatively smaller changes (2-fold) that was chronic hypoxia (< 10 mmHg), whereas ROIs 2 displayed significant fluctuations in pO2 (approximately 18-fold and 12-fold, respectively) that was cycling hypoxia.

Conclusion:

This study demonstrated the phenomenon of re-appearance of cycling hypoxia after irradiation in HT29 and HCT116 tumors by using EPR pO2 imaging. We assess this new approach of cancer imaging provides a powerful tool for studying physiology in vivo using noninvasive imaging biomarkers in preclinical research and we believe the phenomenon of re-appearance of cycling hypoxia after irradiation has great potential for clinical applications for a new perspective in molecular imaging for radiation therapy, and this result indicated the possibility and importance of a new radiation therapy.

Author Disclosure: M. Matsuo: None. F. Hyodo: None. T. Yamaguchi: None. M. Krishna: None. J.B. Mitchell: None.

Masayuki Matsuo, MD, PhD

Gifu University Graduate School of Medical Sciences

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