Design of a cell specific macromolecular contrast agent for higher resolution of magnietic resonance imaging

本研究的目的是建立一种新的成像概念，描绘正常和受损组织之间的病理和/或生理状态的微环境差异。为此，我们新设计了一种智能造影剂，其信号强度仅在较低的pH值下激活。由Gd离子组成的MRI造影剂缩短其周围水分子质子的T1弛豫时间，以增强MRI信号。Gd离子的信号增强活性与试剂的水化行为密切相关。因此，可以通过调节Gd离子的水合行为来改变Gd离子的信号增强活性。我们采用由一对弱酸性和弱碱性聚合物组成的聚离子复合物来设计pH敏感型造影剂。这些带相反电荷的聚离子形成稳定的聚离子复合物，当复合物中的电荷静电等效时，伴随着水分子的释放。本研究制备了一种含Gd离子的pH敏感性聚离子复合物作为智能造影剂，并对其增强MRI信号的pH依赖性进行了评价，结果表明，这种新型MRI造影剂只能在较低pH下特异性增强MRI信号，即使它可能是均匀分布的。由于肿瘤细胞外液比正常组织和血流酸性更强，我们新设计的MRI造影剂的这种可逆的pH依赖性信号转换行为将成为癌症诊断的极好工具。

The purpose of this study was to establish a novel imaging concept which depict micro-environmental differences in pathological and/or physiological states between normal and damaged tissues. For the purpose we newly designed an intelligent contrast agent whose signal intensity is activated only at the lower pH.MRI contrast agents consisting of Gd ions shorten the T1 relaxation time of protons of its surrounding water molecules to enhance MRI signals. The signal enhancement activity of Gd ions is closely related with hydration behavior of the agent. Thus, one can modify the signal enhancement activity of Gd ions by regulating its hydration behavior. We employed polyion complex composed of a couple of weakly acidic and basic polymers to design pH-sensitive contrast agents. These oppositely charged polyions form stable polyion complex accompanying with release of water molecules when the charge in the complex is electrostatically equivalent. But it adsorbs water molecules when the charge balance is disordered by pH variation, In this study, pH-sensitive polyion complex containing Gd ions was prepared as an intelligent contrast agent and its pH-dependent enhancement in MRI signal was evaluated.From the results of this study, this novel MRI contrast agent can specifically enhance MRI signal only at lower pH, even if it might be equally distributed. This reversible pH-dependent signal switching behavior of our newly designed MRI contrast agent will be an excellent tool for cancer diagnosis, since the extracellular fluid of tumor is more acidic than normal tissue and blood stream.