New MR Angiography Agents Using Gd@C60 Nanotechnology

描述（由申请人提供）： 该项目将基于Gd-C60纳米技术创建一类用于血管造影的新型MRI造影剂。含Gd的内嵌金属富勒烯，完全缺乏游离Gd 3+解离，将比传统的线性和大环Gd 3+螯合物更安全;这对于血管造影术所需的半衰期延长的造影剂尤其重要。内嵌金属富勒烯Gd-C60作为一类独特的安全有效的顺磁性血池造影剂的新平台已经显示出相当大的前景。用化合物Gd-C60（C（COOH）2）10获得的初步结果显示其是有效的MRI造影剂（在40 ℃和0.47 T下rl = 4.7 mM-lsec-1）。此外，它是第一个具有良好生物分布的水溶性内嵌金属富勒烯化合物。本项目中合成的新Gd-C60衍生物将基于该化合物，但将带有中性和阴离子带电亲水基团以及其他疏水基团的混合物。这些新化合物的特点是渗透压降低，同时对血清蛋白白蛋白具有高亲和力。这些特征将增加血池停留时间和弛豫率值。物理和弛豫研究将描述这类新的血池MRI对比增强剂的疗效。本研究中产生的新Gd-C60化合物将填补血管造影MR成像应用中的独特利基，例如血管异常的非侵入性检测，同时超过当前Gd螯合物的安全水平。

DESCRIPTION (provided by applicant): This project will create a new class of MRI contrast agents for angiography based on Gd-C60 nanotechnology. Gd-containing endohedral metallofullerenes, having a total lack of free Gd3+ dissociation, will be safer than conventional linear and macrocyclic Gd3+ chelates; this is especially important for contrast agents with the prolonged half-lives needed for angiography. The endohedral metallofullerene Gd-C60 has shown considerable promise as a new platform for a unique class of safe and effective paramagnetic blood-pool contrast agents. Preliminary results obtained with the compound Gd-C60(C(COOH)2)10 revealed it to be an efficient MRI contrast agent (rl = 4.7 mM-lsec-1 at 40 deg C and 0.47 T). In addition, it is the first water soluble endohedral metallofullerene compound with a favorable biodistribution. New Gd-C60 derivatives synthesized in this project will be based on this compound, but will bear a mixture of neutral and anionic charged hydrophilic groups as well as other hydrophobic groups. These new compounds will feature lowered osmolality while having high affinities for the serum protein albumin. These features will increase both blood-pool residence times and relaxivity values. Physical and relaxometric studies will characterize the efficacy of this new class of blood-pool MRI contrast enhancing agents. The new Gd-C60 compounds created in this study will fill a unique niche in angiographic MR imaging applications, for example the non-invasive detection of vascular abnormalities, while exceeding the safety levels of current Gd chelates.