Physiological microenvironment-responsive contrast agent for magnetic resonance imaging

点击翻译按钮获取中文摘要

We have explored intelligent MRI contrast agents which depict microenvironmental differences in pathophysiological states between normal and tumor tissues. MRI contrast agents consisting of Gd ion shorten the T1 -relaxation time of protons in surrounding water molecules to enhance MRI signals. Thus, one can modify the signal enhancement activity of Gd ions by regulating its hydration behavior. In order to regulate hydration behavior of Gd ions in response to pH changes, we have focused on a polyion complex (PIC) composed of a couple of weakly acidic and basic polymers. The stable PIC formation between these oppositely charged polyions at their electrostatically equivalent charge ratio accompanies with the release of water molecules. This complex formation and hydration behavior are significantly affected by pH, since pH change disorders the charge balance in the complex. In previous study, we had demonstrated that T1-relaxation activity of Gd ions loaded in the PIC considerably influenced by pH and suppressed at neutral pH. We further extended the study to estimate potentiality of the PIC-based agent in tumor imaging. We refined the polymer structure of PIC-based agent to thoroughly suppress T1-relaxation activity of the agent at neutral pH. Then, in vivo MRI imaging study with mice bearing colon 26 carcinoma were studied.