Necrosis is a form of cell death, which is related to various serious diseases such as cardiovascular disease, cancer, and neurodegeneration. Necrosis-avid agents(NAAs) selectively accumulated in the necrotic tissues ...Necrosis is a form of cell death, which is related to various serious diseases such as cardiovascular disease, cancer, and neurodegeneration. Necrosis-avid agents(NAAs) selectively accumulated in the necrotic tissues can be used for imaging and/or therapy of related diseases. The aim of this study was to preliminarily investigate necrosis avidity of ^(131)I-evans blue( ^(131)I-EB) and its mechanism. The biodistribution of ^(131)I-EB at 24 h after intravenous administration showed that the radioactivity ratio of necrotic to viable tissue was 3.41 in the liver and 11.82 in the muscle as determined by γ counting in model rats. Autoradiography and histological staining displayed preferential uptake of ^(131)I-EB in necrotic tissues. In vitro nuclear extracts from necrotic cells exhibited 82.3% of the uptake in nuclei at 15 min, as well as 79.2% of the uptake at 2 h after ^(131)I-EB incubation. The DNA binding study demonstrated that evans blue(EB) has strong binding affinity with calf-thymus DNA(CT-DNA)(K_(sv)= 5.08×10~5 L/(mol/L)). Furthermore,the accumulation of ^(131)I-EB in necrotic muscle was efficiently blocked by an excess amount of unlabeled EB.In conclusion, ^(131)I-EB can not only detect necrosis by binding the DNA released from necrotic cells, but also image necrotic tissues generated from the disease clinically.展开更多
基金partially supported by the National Natural Science Foundation of China(Nos.81501536 and 81473120)A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions and the Open Project Program of Jiangsu Key Laboratory of Drug Screening(No.JKLDS2015KF-02)
文摘Necrosis is a form of cell death, which is related to various serious diseases such as cardiovascular disease, cancer, and neurodegeneration. Necrosis-avid agents(NAAs) selectively accumulated in the necrotic tissues can be used for imaging and/or therapy of related diseases. The aim of this study was to preliminarily investigate necrosis avidity of ^(131)I-evans blue( ^(131)I-EB) and its mechanism. The biodistribution of ^(131)I-EB at 24 h after intravenous administration showed that the radioactivity ratio of necrotic to viable tissue was 3.41 in the liver and 11.82 in the muscle as determined by γ counting in model rats. Autoradiography and histological staining displayed preferential uptake of ^(131)I-EB in necrotic tissues. In vitro nuclear extracts from necrotic cells exhibited 82.3% of the uptake in nuclei at 15 min, as well as 79.2% of the uptake at 2 h after ^(131)I-EB incubation. The DNA binding study demonstrated that evans blue(EB) has strong binding affinity with calf-thymus DNA(CT-DNA)(K_(sv)= 5.08×10~5 L/(mol/L)). Furthermore,the accumulation of ^(131)I-EB in necrotic muscle was efficiently blocked by an excess amount of unlabeled EB.In conclusion, ^(131)I-EB can not only detect necrosis by binding the DNA released from necrotic cells, but also image necrotic tissues generated from the disease clinically.
