Endoglin受体靶向多模态纳米探针对早期肝癌显像研究

The fatality rate of HCC in China is the head of every other country. It is imminent to elevate the rate of early diagnosis and early treatment to HCC, and improve the prognosis of HCC therapy. Thus, it is an urgent topic to diagnose HCC in a treatable stage. And find a new diagnostic method to elevate the diagnostic rate of early stage HCC has very important clinical significance. This proposal plans to take anti-endoglin antibody fragment TRC105F(ab)' as target groups, combined with MR imaging and optical imaging groups, to explore the feasibility of non-invasively diagnose early stage HCC with molecular imaging. The nano-probes show their abilities of targeting by the combination of ligands on the probes and the receptors which are over expression in tumor tissue. The distribution of the nano-probes in vivo can be traced by MR imaging and optical imaging systems, so as to reflect the true scopes of tumors. They can enhance the differences between tumors and normal tissues, which could not be present in the regular imaging systems, to describe some tiny neoplasms. Furthermore the dynamic distribution and biocompatibility of the nano-probes in vivo are confirmed through bio-distribution. This proposal will lead to a new progress in the early diagnose of HCC and post-treatment curative effect evaluation of HCC, including detecting of reappearance and microsatellite and so on.

我国肝癌病死率位居各国之首，提高肝癌的早期诊断、早期治疗率，改善肝癌治疗的预后迫在眉睫。因此在可治疗阶段诊断HCC是HCC治疗的紧迫课题，而寻找新的诊断方法，提高肝癌早期诊断率具有重要的临床意义。本项目拟分别以抗endoglin抗体片段TRC105 F(ab)'为靶向基团，结合MRI和光学成像基团，探索将分子影像应用于早期肝癌无创诊断的可行性。目标大分子的靶向性将通过肿瘤组织高表达的受体和大分子运载的配体的结合来实现。大分子在活体内的分布可被磁共振和荧光光学影像重现出来，从而真实反映肿瘤的范围，并通过增强对比，呈现出一些在常规影像成像系统中难以区分的微小肿瘤。而大分子在活体内的动态分布和生物相容性可通过生物分布的方法予以证实。本项目将为肝癌的早期诊断、HCC治疗后疗效评价方面（再发病灶、微卫星病灶的探测等）带来新的进展。