Evans Blue Dye: A Revisit of Its Applications in Biomedicine.

Linpeng Yao,Linpeng Yao,Yicheng Ni,Feng Chen,Feng Chen,Peipei Yu,Peipei Yu,Xing Xue

doi:10.1155/2018/7628037

Abstract

Evans blue (EB) dye has owned a long history as a biological dye and diagnostic agent since its first staining application by Herbert McLean Evans in 1914. Due to its high water solubility and slow excretion, as well as its tight binding to serum albumin, EB has been widely used in biomedicine, including its use in estimating blood volume and vascular permeability, detecting lymph nodes, and localizing the tumor lesions. Recently, a series of EB derivatives have been labeled with PET isotopes and can be used as theranostics with a broad potential due to their improved half-life in the blood and reduced release. Some of EB derivatives have even been used in translational applications in clinics. In addition, a novel necrosis-avid feature of EB has recently been reported in some preclinical animal studies. Given all these interesting and important advances in EB study, a comprehensive revisiting of EB has been made in its biomedical applications in the review.

Highlights

Dating back to the early 20th century, lots of blue dyes were synthesized like Methylene blue, Patent blue, Trypan blue, and so forth, and a comparison of main blue dyes was given in Table 1 [1,2,3,4]
By the late end of the 20th century, Moos and Mollgard found that free dye in plasma caused 60% of neonatal and 20% of the adult animal deaths during their experiments, and the toxicity of free dye led to alteration of the blood-brain barrier (BBB) permeability, while it appeared to be safe when Evans blue (EB) was used as single intravenous injection at a conventional clinical dose [100, 101]
The once widely used EB dye dilution method has gradually been replaced by newer methods, such as radiolabeled albumin and radiolabeled red cells, for the estimation of blood volume and cardiac output

Summary

Introduction

Dating back to the early 20th century, lots of blue dyes were synthesized like Methylene blue, Patent blue, Trypan blue, and so forth, and a comparison of main blue dyes was given in Table 1 [1,2,3,4]. The fluorescent feature of EB dye has been used in various aspects including the characterization of the lymph nodes that drain the liver [13], confirmation of a satisfactory injection into the heart chambers of a zebrafish embryo [14], and observation of the extravasation of the dye from blood vessels into tissues [15,16,17]. Due to its high water solubility and slow excretion, as well as its firm binding to serum albumin, EB is widely used in biomedicine including the estimation of blood volume, the assessment of vascular permeability to macromolecules, the detection of lymph nodes, and the location of the tumor lesions [12, 18,19,20,21,22,23,24]. This article reviews the features of EB and its potential applications in biomedicine

Applications Derived from Albumin-Binding Characteristic of Evans Blue Dye

Use of Evans Blue Dye as a Necrosis-Avid Agent

Radiolabeled Evans Blue Derivatives as Theranostics

Toxicity of Evans Blue Dye

Findings

Conclusion