Physiological microenvironment-responsive contrast agent for magnetic resonance imaging

磁共振成像生理微环境响应造影剂

• 批准号: 12555258
• 负责人: MARUYAMA Atsushi
• 金额: $ 4.35万
• 依托单位: Tokyo Institute of Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12555258/
• 关键词: Gd ion; Polycation; Polyanion; Magnetic resonance imaging; Interpolyelectrolyte complex; pH response; Coacervation; Contrast agents; ガドリヌウムイオン; 高分子電解執複合体; pH応答性; 磁気共鳴画像診断; ポリイオンコンプレックス; 高分子化造影剤

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.

我们已经探索了智能MRI造影剂，其描绘正常和肿瘤组织之间的病理生理状态的微环境差异。由Gd离子组成的MRI造影剂缩短周围水分子中质子的T1弛豫时间以增强MRI信号。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。为了调节Gd离子的水化行为，响应于pH值的变化，我们集中在一对弱酸性和碱性聚合物组成的聚离子配合物（PIC）。这些带相反电荷的聚离子之间以其静电等效电荷比形成稳定的PIC伴随着水分子的释放。这种络合物的形成和水合行为受pH的显著影响，因为pH的变化会扰乱络合物中的电荷平衡。在以前的研究中，我们已经证明，T1弛豫活性的Gd离子加载在PIC相当大的pH值的影响和抑制在中性pH值。我们进一步扩展的研究，以估计潜在的PIC为基础的代理在肿瘤成像。我们改进了PIC基剂的聚合物结构，以彻底抑制该剂在中性pH下的T1弛豫活性。然后，对携带结肠26癌的小鼠进行了体内MRI成像研究。

项目成果

M.Mikawa et al.: "Gd3+-loaded polyion complex for pH depiction with magnetic resonance imaging"J.Biomed.Mater.Res.. 49. 390-395 (2000)

M.Mikawa 等人：“Gd3 负载的聚离子复合物用于用磁共振成像描述 pH”J.Biomed.Mater.Res.. 49. 390-395 (2000)

M.Mikawa, T.Yokawa, N.Miwa, B.Brautigam, T.Akaike, A.Maruyama: "An intelligent MRI contrast agent for tumor sensing"Academic Radiology, supple.. (accepted). (2002)

M.Mikawa、T.Yokawa、N.Miwa、B.Brautigam、T.Akaike、A.Maruyama：“用于肿瘤传感的智能 MRI 造影剂”学术放射学，补充..（已接受）。

朝山章一郎, 赤池敏宏, 丸山厚: "エンドソーム内pHに応答するDNAキャリヤーとしての異種塩基性セグメントを持つポリカチオングラフト共重合体"高分子加工. 50. 106-111 (2001)

Shoichiro Asayama、Toshihiro Akaike、Atsushi Maruyama：“具有异质基本片段的聚阳离子接枝共聚物作为响应内体 pH 的 DNA 载体”聚合物加工。

M.Mikawa, T.Yokawa, N.Miwa, B.Brautigam, T.Akaike, A.Maruyama: "An intelligent MRI contrast agent for tumor sensing"Academic Radiology. 9. S109-S111 (2002)

M.Mikawa、T.Yokawa、N.Miwa、B.Brautigam、T.Akaike、A.Maruyama：“用于肿瘤传感的智能 MRI 造影剂”学术放射学。

A.Maruyama: "Supramolecular design for biological applications ed., N.Yui"CRC Press LLC. 65-82 (2002)

A.Maruyama：“生物应用的超分子设计编辑，N.Yui”CRC Press LLC。