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粒子造影剂进行MRI和SQUID成像。用于成像的对比度增强将由直径约6nm的超顺磁性纳米颗粒提供。造影剂的细胞靶向通过将纳米颗粒与树枝状聚合物支架上的叶酸分子缀合来实现。造影剂的内化是通过高亲和力叶酸受体，其在多种上皮癌中过表达。由于叶酸受体的再循环，细胞可以内化大量的纳米颗粒。纳米颗粒的体外和体内细胞摄取水平将通过磁性测量来确定。对于体内成像，免疫受损小鼠将注射人KB鳞状癌细胞作为疾病模型。引入造影剂后，将进行MR成像。同样，将进行体外和体内超顺磁性颗粒的检测，以确定SQUID成像技术的极限。对于距离SQUID检测器5 cm的肿瘤，估计极限约为1000个细胞。这种方法允许对临床前病变进行成像，并为功能性成像剂的细胞内递送铺平了道路。

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.