Polydisulfide Gd(III) chelates as biodegradable macromolecular magnetic resonance imaging contrast agents.
Polydisulfide Gd(III) chelates as biodegradable macromolecular magnetic resonance imaging contrast agents.
复制标题
多二硫化物GD（III）螯合物作为可生物降解的大分子磁共振成像对比剂。
DOI：
10.2147/nano.2006.1.1.31
复制
发表时间：
2006
影响因子：
8
通讯作者：
中科院分区：
文献类型：
--
作者：
高分子钆（Gd）（III）配合物血液循环时间延长，根据肿瘤血管的高通透性，可优先在实体肿瘤中积累，导致动物模型中磁共振（MR）心血管成像和癌症成像的对比度增强。不幸的是，与这些药物从体内缓慢消除有关的安全问题阻碍了它们的临床发展。多二硫Gd（III）配合物已被设计和开发为可生物降解的大分子磁共振成像（MRI）造影剂，以促进Gd（III）配合物在MRI检查后从体内清除。这些新型药物可以作为体内成像的大分子造影剂，并作为低分子量药物快速排泄。本文综述了新型生物可降解造影剂的基本原理和最新进展。多二硫Gd（III）配合物血液循环时间较长，逐渐降解为小的Gd（III）配合物，经肾滤过迅速排出体外。在动物模型中，这些药物在血池和肿瘤组织中产生有效和持久的体内对比增强，但作为临床使用的低分子量药物，它们表现出最小的Gd（III）组织保留。药剂的结构修饰可以很容易地改变对比增强动力学。聚二硫Gd（III）配合物作为一种安全、有效、可生物降解的大分子MRI造影剂，在心血管和癌症成像以及治疗反应评估方面具有进一步的临床开发前景。
Macromolecular gadolinium (Gd)(III) complexes have a prolonged blood circulation time and can preferentially accumulate in solid tumors, depending on the tumor blood vessel hyperpermeability, resulting in superior contrast enhancement in magnetic resonance (MR) cardiovascular imaging and cancer imaging as shown in animal models. Unfortunately, safety concerns related to these agents’ slow elimination from the body impede their clinical development. Polydisulfide Gd(III) complexes have been designed and developed as biodegradable macromolecular magnetic resonance imaging (MRI) contrast agents to facilitate the clearance of Gd(III) complexes from the body after MRI examinations. These novel agents can act as macromolecular contrast agents for in vivo imaging and excrete rapidly as low-molecular-weight agents. The rationale and recent development of the novel biodegradable contrast agents are reviewed here. Polydisulfide Gd(III) complexes have relatively long blood circulation time and gradually degrade into small Gd(III) complexes, which are rapidly excreted via renal filtration. These agents result in effective and prolonged in vivo contrast enhancement in the blood pool and tumor tissue in animal models, yet demonstrate minimal Gd(III) tissue retention as the clinically used low-molecular-weight agents. Structural modification of the agents can readily alter the contrast-enhancement kinetics. Polydisulfide Gd(III) complexes are promising for further clinical development as safe, effective, biodegradable macromolecular MRI contrast agents for cardiovascular and cancer imaging, and for evaluation of therapeutic response.