Early Assessment of Radiation Treatment at Clinical Field Strength by D2O Administration and Deuterium MRI

Abstract

An accurate and non-invasive assessment of tumor response following treatment is essential. Traditional anatomical imaging techniques are insufficient before a significant morphological change can be observed. Metabolic imaging of molecular processes in the living body is also used. In recent years, deuterium magnetic resonance spectroscopic (MRS) imaging has been demonstrated as an alternative for cancer metabolic imaging by high-field (4-11T) MRI using deuterium-labeled molecules as a contrast agent. The study aim was to evaluate the feasibility of using deuterium MRI 1.5T for tumor visualization and early assessment of the efficacy of three anticancer treatment strategies (radiation and anticancer drugs) in pancreatic cancer model mice given heavy water (D2O) to induce deuterium (2H)-tissue labeling. A MIA PaCa-2 pancreatic cancer model of six BALB/c-nu mice was prepared, and repeated deuterium MRI was performed during the first 10 days after starting free drinking of 30% D2O. We also evaluated 2H accumulation in the tumor after irradiation, bevacizumab administration, or gemcitabine administration of other 20 mice. Additional confirmatory proton MRI, ex vivo metabolic hyperpolarization 13C-MRS and histopathology were performed. 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 in the tumor 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. Deuterium MRI at 1.5T proved feasibility 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 early assessment of radiotherapy and chemotherapy of pancreatic cancer.