Gifu University / Asahi University Hospital Gifu, Gifu
K. Adachi1,2, F. Hyodo3, A. E. Elhelaly4, T. Mori1, T. Mori5, T. Taniguchi2, S. Nakaya2, and M. Matsuo1; 1Department of Radiology, Graduate School of Medicine, Gifu University, Gifu, Japan, 2Department of Radiation Oncology, Asahi University Hospital, Gifu, Japan, 3Department of Pharmacology, Graduate School of Medicine, Gifu University, Gifu, Japan, 4Department of Radiology, Gifu University, Gifu, Japan, 5Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, Gifu, Japan
Purpose/Objective(s): During radiotherapy, inflammatory changes in the intestine are an undesirable biological response. The intestine is also known to be more sensitive to radiation than several other organs. Tissue oxidative stress associated with the generation of reactive oxygen species (ROS) has been shown to play an important role in radiation-induced intestinal inflammation. There is no method to determine the effects of oxidative stress by CT or MRI, and it is difficult to predict early inflammatory effect on the intestine. We have developed non-invasive redox imaging methods using dynamic nuclear polarization (DNP) MRI and carbamoyl PROXYL (CmP) as a redox sensitive bioprobe. The purpose of this study is to develop the redox imaging for monitoring redox status of intestine and to detect the radiation-induced inflammatory damage for early monitoring using in vivo DNP-MRI.Materials/
Methods: Mice were divided into two groups that receiving 10 Gy whole body irradiation and unirradiated groups. The redox reaction of intestinal homogenate solution from irradiated (1hr, 1, 3, 7 days) and unirradiated mice was analyzed by electron spin resonance (ESR). In vivo redox imaging of the lower abdomen including the intestinal area was performed using in vivo DNP MRI after injection of CmP probe solution. After imaging, pathological observations were performed to confirm tissue damage after radiation treatment. Results: The ESR study showed that intestinal tissue has a redox reactivity with CmP. In addition, the redox reaction was enhanced by the addition of NADH which is a substrate of the mitochondrial electron transfer chain. Interestingly, the redox reaction was significantly suppressed by KCN (mitochondrial inhibitor). In vivo DNP MRI clearly visualized the distribution of redox probe(CmP) in the intestinal area and the decay of image intensity was increased even at 1hr after irradiation treatment compared with that of the control. Conclusion: In ESR, mitochondria were involved in the metabolism of CmP, suggesting that changes in CmP metabolism were due to radiation tissue damage. Then, the radiation-induced intestinal inflammatory response was successfully imaged as redox response imaging by in vivo DNP MRI. Furthermore, it is demonstrated that the redox images showed the early change of the intestinal inflammatory response and it is a good biomarker for early monitoring.
