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

• 来源期刊: 药学学报（英文版）
• 关键词: 131I-Evans blue Necrosis avidity Radioactivity DNA binding Necrosis imaging
• 年，卷（期）: 2018,（3）
• 页码范围: 390-400
• 页数: 11页
• 语种: 英文
• DOI: 10.1016/j.apsb.2017.08.002

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 131I-evans blue (131I-EB) and its mechanism. The biodistribution of 131I-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 y counting in model rats. Autoradiography and histological staining displayed preferential uptake of 131I-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 13lI-EB incubation. The DNA binding study demonstrated that evans blue (EB) has strong binding affinity with calf-thymus DNA (CT-DNA) (Ksv = 5. 08×105 L/(mol/L)). Furthermore, the accumulation of 131I-EB in necrotic muscle was efficiently blocked by an excess amount of unlabeled EB. In conclusion, 131I-EB can not only detect necrosis by binding the DNA released from necrotic cells, but also image necrotic tissues generated from the disease clinically.