Topical Gadobutrol Application Causes Fluorescence Intensity Change in RFP-expressing Tumor-Bearing Mice

Natalia Kazachkina,Alexei Bogdanov Jr,Victoria Zherdeva,Asiya Saydasheva,Valery Tuchin,Alexander Savitsky,Irina Meerovich

doi:10.18287/jbpe21.07.020301

Abstract

Optical clearing (OC) allows one to observe tissue structures and metabolic processes occurring in opaque tissues at the depths significantly exceeding the depths that can be reached without OC. Recently, we have shown that gadobutrol is a promising agent for OC of tissues in vivo. The aim of this study was to investigate the effect of time-dependence optical clearing caused by gadobutrol on intensity of fluorescent protein constitutively expressed in subcutaneous tumors in vivo. The measurements were performed in nu/nu mice bearing HEp-2 tumors expressing the red fluorescent protein TagRFP. Gadobutrol was used directly at concentrations 1.0 M aqueous solution or as a 0.7 M aqueous solution containing 5% dimethyl sulfoxide (DMSO). Gadobutrol was applied topically onto the skin above the tumors for 15 min. Tissue fluorescence was measured by using in vivo planar imaging technique. It was shown that the fluorescence intensity of tumors increased by 1.1–1.5 times in different animals under the influence of gadobutrol. The increase in intensity was more pronounced in the case of 0.7 M gadobutrol supplemented with DMSO. Apparently, the observed difference of penetration depths was due to the presence of DMSO in 0.7 M gadobutrol mixture.

Highlights

The planar fluorescence imaging method is based on obtaining of fluorescent images using excitation light source at epi-configuration
The dynamics of fluorescence intensities (FI) changes was dissimilar in the case of 1.0 M gadobutrol and the optical clearing agents (OCA) containing gadobutrol and dimethyl sulfoxide (DMSO)
There was a profound effect of optical clearing (OC) on FI causing an increase of FI of HEp2 tumors expressing red fluorescent TagRFP marker protein

Summary

Introduction

The planar fluorescence imaging method is based on obtaining of fluorescent images using excitation light source at epi-configuration. These methods provide a means for detecting of fluorescent signal in a living animal that reflects specific, mostly disease-related processes, such as the host immune response, inflammation, tumor growth or the presence of pathogens [1,2,3]. G. a combination of fluorescence and magnetic resonance imaging (MRI) In the latter case the use of OCA with paramagnetic properties could be beneficial. One of the potential OCA is gadobutrol with optical clearing properties previously proven in experiments involving optical coherent tomography, spectral and fluorescent microscopy [15]

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