Hydrophobic cyanine dye-doped micelles for optical in vivo imaging of plasma leakage and vascular disruption.

Bálint Botz,Janka Csepregi,Valéria Tékus,Kata Bölcskei,György Sétáló,Zsuzsanna Helyes,Zoltán Sándor,Ágnes Kemény,Erika Pintér,Attila Mócsai,László Kollár

doi:10.1117/1.jbo.20.1.016022

Bálint Botz, Janka Csepregi + Show 9 more

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https://doi.org/10.1117/1.jbo.20.1.016022

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Abstract

Vascular leakage is an important feature of various disease conditions. In vivo optical imaging provides a great opportunity for the evaluation of this phenomenon. In the present study, we focus on the development and validation of a near-infrared (NIR) imaging formula to allow reliable, cost-efficient evaluation of vascular leakage in diverse species using the existing small-animal fluorescence imaging technology. IR-676, a moderately hydrophobic NIR cyanine dye, was doped into self-assembling aqueous micelles using a widely employed and safe nonionic emulsifier (Kolliphor HS 15), and was tested in several acute and chronic inflammatory disease models in both mice and rats. The imaging formula is stable and exerts no acute toxic effects in vitro. It accumulated specifically in the inflamed regions in all models, which could be demonstrated by both conventional epifluorescence imaging, and fluorescence tomography both as a standalone technique and also by merging it with computed tomography scans. Ex vivo verification of dye accumulation by confocal fluorescence microscopy was also possible. The present formula allows sensitive and specific detection of inflammatory plasma leakage in diverse models. Its potential for imaging larger animals was also demonstrated. IR-676-doped micelles offer an excellent opportunity to image inflammatory vascular leakage in various models and species.

Highlights

The interest in near-infrared (NIR) optical in vivo imaging is constantly growing since its debut in the early 2000s,1 and the sensitivity and versatility of the instruments have increased considerably since
The underlying principle of optical in vivo imaging of this phenomenon is based on employing NIR fluorophores, whose particle size is great enough to limit their escaping from healthy vasculature under normal conditions; they retain their ability to Journal of Biomedical Optics
As strong fluorescence was exclusively observed in the wells where micellar IR-676-containing samples were pipetted, which did not propagate in the gel, we can conclude that the formula did not disintegrate even when exposed to strong electric current, and its size prevented it from entering into the gel [Figs. 1(b) and 1(c)]

Summary

Introduction

The interest in near-infrared (NIR) optical in vivo imaging is constantly growing since its debut in the early 2000s,1 and the sensitivity and versatility of the instruments have increased considerably since . There is only a narrow range of reliable contrast agents currently available, and this is especially true for fluorescence markers dedicated to image plasma leakage from diseased vasculature. Most of these probes either suffer from low contrast and signal-to-background ratio, or have tremendous operational costs, thereby limiting large-scale imaging, and in general, do not enable studies involving research animals larger than mice. It is not surprising that noninvasive, longitudinal, real-time evaluation of these processes provides a great opportunity to estimate the extent and characteristics of these conditions, for which NIR optical imaging is an excellent alternative in preclinical settings compared to other modalities (computed tomography etc.) due to the availability of tabletop instruments and lack of ionizing radiation.[4]

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