Targeted Magnetic Contrast Agent for MRI / SQUID Imaging

描述(由申请人提供)： 我们建议使用靶向磁性纳米造影剂进行MRI和SQUID成像。成像的对比度增强将由直径约6纳米的超顺磁性纳米颗粒提供。造影剂的细胞靶向是通过将纳米颗粒连接到树枝状大分子支架上的叶酸分子来完成的。造影剂的内化是通过高亲和力的叶酸受体实现的，该受体在各种上皮性癌症中过度表达。由于叶酸受体的循环，细胞可以内化大量的纳米颗粒。在体外和体内细胞对纳米颗粒的摄取水平将通过磁性测量来确定。为了进行体内成像，免疫缺陷小鼠将注射人KB鳞状癌细胞作为疾病模型。在引入造影剂后，将进行磁共振成像。同样，将在体外和体内对超顺磁性粒子进行检测，以确定鱿鱼成像技术的最终极限。据估计，距鱿鱼探测器5厘米的肿瘤细胞数约为1000个。这种方法允许临床前病变的想象，并为功能显像剂的细胞内输送铺平了道路。

DESCRIPTION (provided by applicant): We propose to perform MRI and SQUID imaging using targeted magnetic nanoparticle contrast agents. The contrast enhancement for the imaging will be provided by superparamagnetic nanoparticles approximately 6 nm in diameter. Cellular targeting of the contrast agent is accomplished by conjugating the nanoparticles to folate molecules on a dendrimer scaffold. Internalization of the contrast agent is through the high-affinity folate receptor, which is overexpressed in a variety of epithelial cancers. Due to recycling of the folate receptor, the cells can internalize high numbers of nanoparticles. In vitro and in vivo cellular uptake levels of the nanoparticles will be determined by magnetic measurements. For in vivo imaging, immune compromised mouse will be injected with human KB squameous carcinoma cells as a disease model. After introduction of the contrast agent, MR imaging will be performed. Similarly, detection of the superparamagnetic particles both in vitro and in vivo will be performed to determine the ultimate limits of the SQUID imaging technique. Estimates place the limit at approximately 1000 cells for a tumor 5 cm from the SQUID detector. This approach allows the imagining of pre-clinical lesions, and paves the way for intracellular delivery of functional imaging agents.