Deuterium Magnetic Resonance Imaging Using Deuterated Water-Induced 2H-Tissue Labeling Allows Monitoring Cancer Treatment at Clinical Field Strength

Author:

Asano Hirofumi12ORCID,Elhelaly Abdelazim Elsayed34ORCID,Hyodo Fuminori15ORCID,Iwasaki Ryota6ORCID,Noda Yoshifumi1ORCID,Kato Hiroki1ORCID,Ichihashi Koki7ORCID,Tomita Hiroyuki7ORCID,Murata Masaharu8ORCID,Mori Takashi6ORCID,Matsuo Masayuki1ORCID

Affiliation:

1. 1Department of Radiology, Gifu University, Gifu, Japan.

2. 2Department of Radiological Technology, Central Japan International Medical Center, Gifu, Japan.

3. 3Department of Radiology, Frontier Science for Imaging, Gifu University, Gifu, Japan.

4. 4Department of Food Hygiene and Control, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt.

5. 5Center for One Medicine Innovative Translational Research (COMIT), Institute for Advanced Study, Gifu University, Gifu, Japan.

6. 6Joint Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, Gifu, Japan.

7. 7Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan.

8. 8Center for Advanced Medical Open Innovation, Kyushu University, Fukuoka, Japan.

Abstract

Abstract Purpose: An accurate and noninvasive assessment of tumor response following treatment other than traditional anatomical imaging techniques is essential. Deuterium magnetic resonance spectroscopic (MRS) imaging has been demonstrated as an alternative for cancer metabolic imaging by high-field MRI using deuterium-labeled molecules. The study aim was to use 2H tissue labeling and deuterium MRI at clinical field strength for tumor visualization and assessment of three anticancer therapies in pancreatic cancer model mice. Experimental Design: MIA PaCa-2 pancreatic carcinoma and C26 colorectal carcinoma models of BALB/c-nu mice was prepared, and repeated deuterium MRI was performed during the first 10 days of free drinking of 30% D2O to track 2H distribution in tissues. 2H accumulation in the tumor after irradiation, bevacizumab administration, or gemcitabine administration was also measured in MIA PaCa-2–bearing mice. Confirmatory proton MRI, ex vivo metabolic hyperpolarization 13C-MRS, and histopathology were performed. Results: The mouse's whole-body distribution of 2H was visible 1 day after drinking, and the signal intensity increased daily. Although the tumor size did not change 1 and 3 days after irradiation, the amount of 2H decreased significantly. The 2H image intensity of the tumor also significantly decreased after the administration of bevacizumab or gemcitabine. Metabolic hyperpolarization 13C-MRS, proton MRI, and 2H-NMR spectroscopy confirmed the efficacy of the anticancer treatments. Conclusions: Deuterium MRI at 1.5T proved feasible to track 2H distribution throughout mouse tissues during D2O administration and revealed a higher 2H accumulation in the tumor xenografts. This research demonstrated a promising successful method for preliminary assessment of radiotherapy and chemotherapy of cancer.

Funder

Japan Agency for Medical Research and Development

Japan Society for the Promotion of Science

MEXT Quantum Leap Flagship Program

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Oncology

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