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

Natalia I. Kazachkina
Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russian Federation

Victoria V. Zherdeva (Login required)
Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russian Federation

Asiya N. Saydasheva
Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russian Federation

Irina G. Meerovich
Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russian Federation

Valery V. Tuchin
Research-Educational Institute of Optics and Biophotonics, Saratov State University, Russian Federation
Interdisciplinary Laboratory of Biophotonics, National Research Tomsk State University, Russian Federation
Laboratory of Laser Diagnostics of Technical and Living Systems, Institute of Precision Mechanics and Control of the Russian Academy of Sciences, Saratov, Russian Federation

Alexander P. Savitsky
Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russian Federation

Alexei A. Bogdanov Jr.
Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russian Federation
Department of Radiology, University of Massachusetts Medical School, Worcester, MA, USA


Paper #3398 received 28 Dec 2020; revised manuscript received 28 Jan 2021; accepted for publication 29 Jan 2021; published online 27 Mar 2021.

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.

Keywords

fluorescence in vivo imaging; optical clearing; MRI-contrast agents; DMSO; genetically encoded fluorescent proteins; subcutaneous tumor; nude mice

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