^(131)I-Evans blue: evaluation of necrosis targeting property and preliminary assessment of the mechanism in animal models

摘要

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.