Metabolic Imaging in the Study of Oncological Processes (Review)

Abstract

There have been reviewed the main approaches to the study of energy metabolism in cancer cells, based on fluorescent imaging of NADH and FAD cofactors. The term "metabolic imaging" covers a range of modern fluorescent techniques for detecting NADH and FAD according to fluorescence intensity and/or lifetime. These cofactors play an important role in energy metabolism reactions acting as electron carriers and, being fluorescent, serve as a basis for metabolic process analysis in living cells and tissues without the use of additional coloring agents. Particular attention is paid to metabolic changes associated with carcinogenesis. Numerous examples of metabolic imaging application in cell cultures in vitro, animal and human tumors in vivo, as well as in patients' tumor biopsy samples have demonstrated its being highly demanded for biomedical research in the area of oncology.Key words: metabolic imaging; energy metabolism; fluorescence lifetime; redox ratio; NADH; FAD; oxidative phosphorylation; glycolysis; tumor cells.For contacts: Mariya M. lukina, e-mail: kuznetsova.m.m@yandex.ru Cells need energy to maintain homeostasis. All processes of cell activity, such as generating concentration gradients, cytoskeleton movement, DNA repair, transcription, translation and vesicular transport, are energy-dependent. Energy metabolism of normal cells is known to differ significantly from cell metabolism in case of a disease. Therefore, the metabolic status can serve as an indicator for diagnosis and visualization of response to pathological process treatment. Taking into account high incidence of oncological diseases, assessment of metabolic phenotype of tumor cells is particularly urgent.Development of optical visualization technologies has provided the possibility of noninvasive analysis of metabolic cofactors NADH and FAD in living tumor cells at high spatial resolution (up to several hundred Metabolic Imaging in the Study of Oncological Process nanometers) without using additional coloring agents and with no significant effect on biochemical and physiological condition of cells. The term "metabolic imaging" covers a range of modern fluorescent techniques which allow visualizing NADH and FAD according to their fluorescence intensity and/or lifetime.The present review characterizes the properties of energy metabolism in cancer cells, describes the two key approaches to the assessment of metabolic status: analysis of cofactor fluorescence intensity ratio (redox ratio) and their fluorescence lifetime. There have been presented numerous examples of metabolic imaging application in cell cultures in vitro, animal and human tumors in vivo, as well as in patients' tumor biopsy samples.

Label‐free imaging and spectroscopy for early detection of cervical cancer

“…Hypoxia was found in many solid tumors due to the atypical structure of microcirculatory vessels, long distances between blood vessels and tumor cells [34]. NADH is largely formed during glycolysis and FAD mainly during oxidative phosphorylation.…”

“…NADH is largely formed during glycolysis and FAD mainly during oxidative phosphorylation. However, it has been established that energy metabolism of tumor cells presents a balance between glycolysis and oxidative phosphorylation and the ratio of ATP production by glycolysis and oxidative phosphorylation can vary significantly depending on the environment [34]. Hypoxia was found in many solid tumors due to the atypical structure of microcirculatory vessels, long distances between blood vessels and tumor cells [34].…”

“…Generally, neoplastic cells have different metabolic conditions for rapid cell proliferation relative to normal cells. Hypoxia was found in many solid tumors due to the atypical structure of microcirculatory vessels, long distances between blood vessels and tumor cells [34]. As a result of lower oxygen level, oxidative phosphorylation decreases, and there is a reduced demand for NADH in the electron transport chain [40].…”

“…Most of the studies reported the intensity difference between healthy and cancerous samples, but the sensitivities in the literature are variable, ranging from 62% to 92% [26,33]. Since NADH and FAD are the only electron carriers that exhibit native fluorescence, the ratio of their fluorescence can be used to monitor the metabolic status of cells and tissues [34]. Comparing with the intensity, the native fluorescence spectrum feature, such as the ratio of NADH and FAD, is more robust to provide the metabolic changes between normal and neoplastic cells.…”

“…NADH is the primary donor and FAD is the primary electron and proton acceptor in mitochondrial respiratory chain. Since NADH and FAD are the only electron carriers that exhibit native fluorescence, the ratio of their fluorescence can be used to monitor the metabolic status of cells and tissues [34].…”