靶向Vimentin/SSTR双靶点诊疗一体化探针用于特发性肺纤维化的早期诊疗

Idiopathic pulmonary fibrosis (IPF) is a severe progressive fibrotic hyperplasia with a survival of only 3 to 5 years. Fibroblasts, as the main cells of collagen produced in IPF, are important targets for the diagnosis and treatment of IPF. We propose to develop a dual-target probe 99mTc-GlcNAc-PEI-TATE, targeting Vimentin by N-acetylglucamine (GlcNAc), and targeting SSTR by 3-tyrosyl-octreotide (3-Tyr-octreotide, TATE) , polyethyleneimine (PEI) as a linker and 99mTc-labeled group, and establish single photon emission computed tomography (SPECT) imaging methods for the early diagnosis and diagnosis of IPF and loadTGFβ-1 siRNA for targeted therapy of IPF , and achieve the aim of theranostics of IPF, finally.

特发性肺纤维化(IPF)是一种严重的进行性纤维化增生，患者的存活期只有3~5年。成纤维细胞作为IPF中产胶原蛋白的主要细胞，是IPF诊断和治疗的重要靶点。我们以成纤维细胞表面的波形蛋白（Vimentin）、生长抑素受体（SSTR）为双靶点，通过N-乙酰葡糖胺（GlcNAc）靶向Vimentin，3-酪氨酰基-奥曲肽（3-Tyr-octreotide, TATE）靶向SSTR，聚乙烯亚胺（PEI）为连接骨架和99mTc标记基团，合成双靶点诊疗一体化探针—99mTc-GlcNAc-PEI-TATE，建立单光子发射计算机断层成像（SPECT）成像方法用于IPF的早期诊断，通过装载转化生长因子β-1（TGFβ-1）siRNA用于IPF的靶向治疗，最终实现IPF的诊疗一体化。

有证据支持波形蛋白（Vimentin）在特发性肺纤维化（IPF）中的表达增加。我们以Vimentin靶向的探针—99mTc-N-乙酰氨基葡萄糖-聚乙烯亚胺（99mTc-NAG-PEI）通过单光子发射计算机断层成像（SPECT）可视化研究IPF，并使用NAG-PEI/TGF-β1-siRNA进行了SPECT成像指导下的靶向基因治疗。设计并合成Vimentin靶向诊疗一体化探针99mTc-NAG-PEI/siRNA，结合分子影像学的可视化优点，首次提出通过靶向Vimentin进行IPF的无创、实时、精准诊疗；同时，提出通过SPECT显像联合组织学分析的IPF评估策略，进一步确认SPECT探针用于IPF诊疗的可行性。