Mohs Aaron M, Wang Xinghe, Goodrich K Craig, Zong Yuda, Parker Dennis L, Lu Zheng-Rong
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
Bioconjug Chem. 2004 Nov-Dec;15(6):1424-30. doi: 10.1021/bc049828r.
Biodegradable PEGylated Gd-DTPA l-cystine copolymers, PEG-g-poly(GdDTPA-co-l-cystine), were prepared and tested as a blood pool contrast agent in mice. The biodegradable macromolecular agent was designed to be broken down into smaller Gd complexes by endogenous thiols via the disulfide-thiol exchange reaction to facilitate the clearance of Gd complexes after the contrast-enhanced MRI examination. Gd-DTPA l-cystine copolymers were synthesized by condensation polymerization of l-cystine and DTPA-dianhydride in water followed by chelating with Gd(OAc)(3). MPEG-NH(2) (MW = 2000) was then conjugated to the polymeric backbone in different ratios. The macromolecular contrast agent was readily degraded with the incubation of l-cysteine. It also demonstrated superior contrast enhancement in the heart and blood vessels as compared to a low molecular weight control agent, Gd-(DTPA-BMA). At 1 h postcontrast, the PEGylated macromolecular agent still showed prominent enhancement, while little contrast enhancement was detectable in the blood pool by the control agent. PEG-g-poly(GdDTPA-co-l-cystine) shows promise as an MR blood pool imaging agent.
制备了可生物降解的聚乙二醇化钆-二乙三胺五乙酸- l -胱氨酸共聚物（PEG - g -聚（钆二乙三胺五乙酸 - 共 - l -胱氨酸）），并在小鼠体内作为血池造影剂进行了测试。这种可生物降解的大分子造影剂被设计成通过二硫键 - 硫醇交换反应，被内源性硫醇分解成较小的钆配合物，以便在增强磁共振成像检查后促进钆配合物的清除。钆 - 二乙三胺五乙酸 - l -胱氨酸共聚物是通过在水中使l -胱氨酸与二乙三胺五乙酸二酐缩聚，然后与醋酸钆（Gd(OAc)₃）螯合而合成的。随后将甲氧基聚乙二醇胺（MPEG - NH₂，分子量 = 2000）以不同比例连接到聚合物主链上。该大分子造影剂在与l -半胱氨酸孵育时很容易降解。与低分子量对照剂钆 -（二乙三胺五乙酸 - BMA）相比，它在心脏和血管中也表现出优异的造影增强效果。在造影后1小时，聚乙二醇化大分子造影剂仍显示出明显的增强，而对照剂在血池中几乎检测不到造影增强。PEG - g -聚（钆二乙三胺五乙酸 - 共 - l -胱氨酸）有望成为一种磁共振血池成像剂。
