New MR Angiography Agents Using Gd@C60 Nanotechnology

描述(由申请人提供)： 该项目将创造一种基于Gd-C60纳米技术的用于血管成像的新型MRI造影剂。含Gd的金属富勒烯完全没有游离的Gd3+解离，将比传统的线型和大环型Gd3+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。体内金属富勒烯Gd-C60作为一种独特的安全有效的顺磁性血池造影剂的新平台显示出巨大的潜力。化合物Gd-C60(C(COOH)2)10的初步结果表明，它是一种有效的MRI造影剂(在40℃和0.47T时rl=4.7 mm-lsec-1)。此外，它还是第一个具有良好生物分布的水溶性面体内金属富勒烯化合物。本项目合成的新的Gd-C60衍生物将以该化合物为基础，但将含有中性和阴离子带电的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有很高的亲和力。这些功能将增加血池停留时间和松弛系数。物理和松弛测量研究将表征这种新型血池MRI造影剂的疗效。在这项研究中创造的新的Gd-C60化合物将填补血管成像磁共振成像应用中的一个独特的利基市场，例如血管异常的非侵入性检测，同时超过目前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.