POLYCHELATING AGENT INCORPORATION LIPOSOMES & MICELLES

一种新型的聚合物探针能够螯合多个金属原子（在，钆）和适合于纳入脂质体和胶束将在体外合成和测试。一种新的分子代表低分子量DTPA-聚赖氨酸通过其N-末端连接到脂质锚，NGPE-PE（DTPA-PLL-PE）。在初步实验中，我们在此证明，与经由已知的亲膜性DTPA-SA和DTPA-PE负载Gd的脂质体相比，含有3摩尔%的新的膜结合多螯合剂并负载Gd的脂质体具有增强的对水质子的弛豫性。脂质体将用不同含量的DTPA-PLL-PE和聚乙二醇-PE（PEG-PE）制备，并在其对血浆的弛豫性和稳定性方面进行优化。将制备含有可变量DTPA-PLL-PE的PED-PE基胶束。它们的弛豫性和稳定性将在负载钆后进行研究。拟定的商业应用：目前尚无用于磁共振成像的血管成像剂上市。每年有800万例冠状动脉疾病，其中估计有100万次扫描。MRI血管造影造影剂仅在美国就有很大的潜在市场。

A novel polymeric probe capable of chelating multiple metal atoms (In, Gd) and suitable for the incorporation into liposomes and micelles will be synthesized and tested in vitro. A new molecule represents low-molecular- weight DTPA-polylysine linked via its N-terminus to a lipid anchor, NGPE-PE (DTPA-PLL-PE). In a preliminary experiment, we demonstrated here that liposomes containing 3 mole % of new membrane- bound polychelator and loaded with Gd possess enhanced relaxivity for water protons when compared with liposomes loaded with Gd via known membranotropic DTPA-SA and DTPA-PE. Liposomes will be prepared with variable contents of DTPA-PLL-PE and polyethylene glycol-PE (PEG-PE) and optimized in terms of their relaxivity and stability towards blood plasma. PED-PE-based micelles will be prepared containing variable quantities of DTPA-PLL-PE will be prepared. Their relaxivity and stability will be studied upon loading with Gadolinium. PROPOSED COMMERCIAL APPLICATIONS: Currently there are no vascular imaging agents marketed for Magnetic Resonance Imaging. There are 8 million cases of coronary artery disease per year of which there are one million scans estimated for this population. A MRI angiography contrast agent would have a large potential market in the USA alone.