多模式分子影像探针的设计制备与影像研究

Molecular imaging probes stand a key position in the development of molecular imaging. Affibody’s high affinity and specificity toward target proteins, small size and quick/fast blood and renal clearance make it possible for promising clinical applications. However, there still exist some problems about Affibody Molecular imaging Probes, such as their low tumor uptake and main renal clearance, et al.. Here, we first design and construct a series of HER2 tumor-associated, affibody targeted, PAMAM linked NIRF /PET dual modal imaging probe in the world, for the purpose of raising tumor uptake and balance the clearance ways. The factors and mechanisms to effect tumor uptake and Bio-D performance will be analyzed by changing probe’s size/hydrophilicity/hydrophobicity/numbers of affibody, and those probe’s in vitro cell stain and in vivo nude mouse imaging as well as ex vivo NIRF imaging will be studied. The probe with well performance will be expected by optimizing the structure of probes based on our studies.

分子探针是分子影像学发展的核心课题之一。亲和体具有分子尺寸小，与靶蛋白亲和性和特异性高，快速的血液、肾脏清除率等优势，但存在肿瘤摄取量不高、主要依靠肾脏途径清除的问题。. 本项目以提高亲和体探针肿瘤摄入量、改善清除途径为目标，首次设计建立以亲和体为靶向分子，PAMAM为连接体，成像优势互补的PET/NIRF双模式分子影像探针。通过对探针进行一系列in vitro、in vivo研究，探索PAMAM-亲和体为核心的PET/NIRF双模式探针中连接体大小、亲疏水性、靶向分子接入量对探针肿瘤摄入量、以及清除速率清除途径等药代动力学行为的影响及机制。通过优化探针结构，优选出性能最佳的分子影像探针。

分子探针是分子影像学发展的核心课题之一。亲和体具有分子尺寸小，与靶蛋白亲和性和特异性高，快速的血液、肾脏清除率等优势，但存在肿瘤摄取量不高、主要依靠肾脏途径清除的问题。.本课题首次设计、合成并优化了系列分子影像探针，获得了更高的亲和体探针肿瘤摄入量、更优的清除途径。开展并完成了这些探针的一系列in vitro、in vivo研究，发现了探针中连接体大小、亲疏水性、靶向分子接入量对探针肿瘤摄入量、以及清除速率清除途径等药代动力学行为有很大影响并分析总结了其中的机制，为多模式分子影像探针的临床应用打下了坚实基础。.