Radioactive Molecular Probes For Accurate Diagnosis And Treatment Of Hepatic And Pulmonary Fibrosis By SPECT Imaging

Fibrosis is characterized by the deposition of extracellular matrix proteins(ECM)during chronic injury,which is prevalent in most of the chronic diseases.Liver fibrosis is caused by the accumulation of ECM resulting from the collapse of liver lobules,produces hepatocellular dysfunction,and finally develops to liver cirrhosis or even liver cancer.The early stage of liver fibrosis is relatively easy to reverse,but when fibrosis develops to cirrhosis,effective treatment is left only liver transplantation.Idiopathic pulmonary fibrosis is a fibrotic disease of unknown etiology with a very poor prognosis.Patients generally die within 3 to 5 years after diagnosis.It has important implications to develop a non-invasive method of diagnosis of fibrosis.In this experiment,SPECT/CT fusion imaging was used to assess and staging liver and pulmonary fibrosis using two polymer-based and fibrosis-related SPECT probes.And then,we investigated whether these SPECT probes could be used for assessing fibrosis and monitoring of drug treatment response.The main works were described as following:1.The application of the ASGP-R targeted radioprobe 99mTc-p(VLA-co-VNI)in staging of liver fibrosis was evaluated in a CCl4-induced mice model.A new index-liver uptake value(LUV)was proposed for the quantification of the radioactive uptake of the liver in SPECT imaging.We proved that LUV value could be used for the accurate staging of liver fibrosis.Then,we evaluated the ues of 99mTc-p(VLA-co-VNI)SPECT/CT imaging in monitoring the response of TanIIA treatement in the liver fibrotic mice.2.We developed a new hepatic stellate cell targeted probe—99mTc-GlcNAc-PEI.99mTc-GlcNAc-PEI has a high affinity with the desmin and vimentin on the surface of activated hepatic stellate cells.We obtained high-quality liver images with SPECT/CT imaging in the fibrotic mice.99mTc-GlcNAc-PEI SPECT/CT was usefull in evaluating hepatic fibrosis and we confirmed that it could be used in the diagnosis of early hepatic fibrosis.Then,we evaluated the ues of 99mTc-GlcNAc-PEI SPECT/CT imaging in monitoring the response to the treatment of chlorophosphate liposomes in the fibrotic mice.3.The application of 99mTc-GlcNAc-PEI in idiopathic pulmonary fibrosis was evaluated.In the bleomycin-induced fibrotic mice,the pulmonary uptake of 99mTc-GlcNAc-PEI in the BM-7d group was significantly different with the control group.This suggestsed 99mTc-GlcNAc-PEI SPECT imaging could be used for the diagnosis of early pulmonary fibrosis.At the same time,GlcNAc-PEI was loaded with siRNA for gene therapy to realize the integration of diagnosis and treatment.