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REVIEW: Sensors for Proteolytic Activity Visualization and Their Application in Animal Models of Human Diseases

A. A. Bogdanov, Jr.1,2,3,a*, I. D. Solovyev2,4, and A. P. Savitsky2,4

1University of Massachusetts Medical School, Department of Radiology, Laboratory of Molecular Imaging Probes, MA 01655, Worcester, USA

2A. N. Bach Institute of Biochemistry, Federal Research Center “Fundamentals of Biotechnology”, Russian Academy of Sciences, Laboratory of Molecular Imaging, 119071 Moscow, Russia

3Lomonosov Moscow State University, Faculty of Bioengineering and Bioinformatics, 119991 Moscow, Russia

4A. N. Bach Institute of Biochemistry, Fundamentals of Biotechnology Federal Research Center, Russian Academy of Sciences, Laboratory of Physical Biochemistry, 119071 Moscow, Russia

* To whom correspondence should be addressed.

Received October 6, 2018; Revised October 6, 2018; Accepted October 6, 2018
Various sensors designed for optical and photo(opto)acoustic imaging in living systems are becoming essential components of basic and applied biomedical research. Some of them including those developed for determining enzyme activity in vivo are becoming commercially available. These sensors can be used for various fluorescent signal detection methods: from whole body tomography to endoscopy with miniature cameras. Sensor molecules including enzyme-cleavable macromolecules carrying multiple quenched near-infrared fluorophores are able to deliver their payload in vivo and have long circulation time in bloodstream enabling detection of enzyme activity for extended periods of time at low doses of these sensors. In the future, more effective “activated” probes are expected to become available with optimized sensitivity to enzymatic activity, spectral characteristics suitable for intraoperative imaging of surgical field, biocompatibility and lack of immunogenicity and toxicity. New in vivo optical imaging methods such as the fluorescence lifetime and photo(opto)acoustic imaging will contribute to early diagnosis of human diseases. The use of sensors for in vivo optical imaging will include more extensive preclinical applications of experimental therapies. At the same time, the ongoing development and improvement of optical signal detectors as well as the availability of biologically inert and highly specific fluorescent probes will further contribute to the introduction of fluorescence imaging into the clinic.
KEY WORDS: sensor molecules, optical and photo(opto)acoustic imaging, fluorescent signal detection

DOI: 10.1134/S0006297919140013