||Non-invasive Tumor Redox Imaging Using Magnetic Resonance Imaging
Hyodo, Fuminori ,
Ken-ichiro, Matsumoto ,
Utsumi, Hideo ,
B Mitchell, JamesKrishna, Murali
Anatomic imaging techniques such as CT, MRI provide physical description of the region of interest with exquisite spatial resolution. A priori determination of tissue redox status can be helpful in the clinical setting, especially in cancer treatment, where information pertaining to tumor physiology can help in the choice of appropriate treatment strategies. We report a method of imaging tissue/tumor redox status information with MRI using a novel class of redox-sensitive paramagnetic contrast agents, called the nitroxyl radicals. Nitroxyl radicals are organic free radicals, which are non-toxic and can mimic antioxidant enzymes such as superoxide dismutase, catalase in addition to scavenging free radicals. In the case of nitroxyl radical, in addition to pharmacokinetics of the probe, the contrast is also governed by the tissue redox status. Using nitroxyl radical and opens the possibility to exploit the high reactivity of nitroxyl radical to monitor tissue redox status, which can be co-registered to anatomic images. In this study, several nitroxyl radicals were compared using SPGR(spoiled-gradient echo) based T1-weighted MRI to assess the suitability of nitroxyl radical for in vivo redox MR imaging. MRI based intensity change (due to reduction and clearance of total probe) of nitroxyl radical in tumor was compared with those of normal tissue. The MR images of all nitroxyl radicals showed similar concentration dependence. The MR image in tumor showed enhanced image intensity depending on the nitroxyl radical concentration. The in vivo reduction rate of nitroxyl radical in tumor tissue was clearly faster than that of normal. The fast reduction of nitroxyl radical in tumor is consistent with the hypoxic environment with strong reductive capacity compared to normal tissue. Therefore this SPGR based MRI with nitroxyl radical can obtain redox status with high spatial and temporal resolution. Such information will help in evaluating hypoxic regions of a tumor/cancer and planning therapy.
15th International Congress of Radiation Research (ICRR 2015)