Insights into metabolic aspects of tumor growth with fluorescence and phosphorescence time-resolved techniques
Marina SHIRMANOVA1, Maria LUKINA1, Liubov SHIMOLINA1, Vladislav SHCHESLAVSKIY1, Varvara DUDENKOVA1, Vladimir ZAGAINOV2, Anna ORLOVA3, Ilya KRITCHENKOV4, and Elena ZAGAYNOVA1
1Institute of Experimental Oncology and Biomedical Technologies, Privolzhskiy Research Medical University, Russia
2Volga District Medical Center, Russia
3Institute of Applied Physics RAS, Russia
4Chemistry Department, Saint Petersburg State University, Russia
Abstract
Cancer cells and tissues are different in many ways from other cells and tissues in the body. The key features of cancer are abnormal cell growth, invasion and metastasis, metabolic plasticity with a high contribution of glycolysis to energy production, hypoxia tolerance, genetic and phenotypic heterogeneity.
In our studies, we investigate some biological characteristics of tumors using fluorescence lifetime imaging (FLIM) and phosphorescence lifetime imaging (PLIM). Currently available time-resolved imaging systems enable to visualize fluorescence and phosphorescence from a micro- to a macroscopic scale, which opens the opportunity to explore cancer from cellular to a whole tumor level.
FLIM enables the detection of endogenous fluorescence from the metabolic coenzymes reduced nicotinamide adenine dinucleotide (phosphate) NAD(P)H and oxidized flavin adenine dinucleotide (FAD). FLIM of the autofluorescence has already proved to be a useful approach for quantitative assessments cellular metabolic state. The results of our studies on animal tumor models and patients’ tumor samples demonstrate the possibility to detect metabolic differences between tumor and healthy tissue on the basis of NAD(P)H fluorescence lifetime parameters [1,2]. An important feature of patients’ tumors was a significant degree of metabolic heterogeneity at the cellular level.
PLIM can be used to assess tissue oxygen by measuring phosphorescence lifetime of oxygen-sensitive synthetic probes. Phosphorescence intensity and lifetime decrease with the increase of O2 concentration due to quenching of phosphorescence by molecular O2. Using Ir(III)-based complexes, we observed lower oxygen content in a mouse tumor than in a muscle in vivo [3,4] and decreased oxygen level in a tumor after chemotherapy with topoisomerase I inhibitor irinotecan.
In general, the specifics of tumor metabolism identified by FLIM of NAD(P)H and PLIM with chemical sensors open up novel opportunities for tumor prognosis and monitoring of therapy.
REFERENCES
[1] V. Shcheslavskiy, et al., Opt. Lett., 2018, 43(13), 3152–3155
[2] M. Lukina et al. Methods Appl. Fluoresc. 8 (2020) 014002
[3] M. Lukina et al. Opt. Lett., 42(4), 2017
[4] A. Solomatina et al. RSC Adv.,2018, 8, 17224
The studies are supported by the Russian Science Foundation (project # 20-65-46018, FLIM; project #18-73-10021, PLIM).
Speaker
Marina Shirmanova
Privolzhskiy Research Medical University
Russia
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