Noninvasive Redox Imaging of Tumor Redox Status for Early Detection of Radiation Response using In Vivo DNP-MRI

Abstract

Dynamic nuclear polarization (DNP)-MRI is a technology that uses the energy of free radicals (electron spins) to increase the sensitivity of MRI. We have previously succeeded in visualizing redox status in tumors after radiation treatment in pancreatic cancer transplanted mouse models by redox imaging using in vivo DNP-MRI. The purpose of this study was to clarify the dynamics of tumor redox stats for early detection of treatment response after irradiation. Mice (Balb / C) were transplanted with a pancreatic cancer cell line (MIA PaCa-2) in the right lower limb. When the tumor diameter reached 500 mm3, the control group (n = 4) and the irradiation group (n = 4), and DNP-MR imaging with carbamoyl-PROXYL (CmP) were performed. Thereafter, radiation treatment (2, 5, 10 Gy) by Linac were performed. Second DNP-MR imaging were performed 24 hours after irradiation. Image intensity in tumor region was obtained from pharmacokinetic DNP images. The decay rate of DNP enhancement area induced by CmP in the tumor were calculated. The tumor diameter was measured twice a week from the first DNP-MRI imaging to the 21st day. From the DNP images after CmP administration, the distribution of CmP in the tumor significantly expanded after irradiation. The redox metabolism calculated from the decay rate of kinetic DNP enhanced images at 24 hours after irradiation was significantly lower in all irradiation groups than that of control group. The tumor growth of all irradiated groups was stopped up to 3 days after irradiation, after which a clear dose-dependent change of tumor size was observed compared to the control group. This study revealed that redox metabolism in tumors changed from the early stage of irradiation prior to morphological changes. If the redox metabolism in tumor tissue was significantly reduced after irradiation, the tumor growth rate might be expected to be reduced. Our results suggest that the reduction of tumor growth by irradiation on a mouse model of pancreatic cancer transplantation can be predicted by evaluating the decay rate of CmP using in vivo DNP-MRI.