Bioluminescent-based imaging and quantification of glucose uptake in vivo

• Published in: Nature methods Vol. 16; no. 6; pp. 526 - 532
• Main Authors: Maric, Tamara, Mikhaylov, Georgy, Khodakivskyi, Pavlo, Bazhin, Arkadiy, Sinisi, Riccardo, Bonhoure, Nicolas, Yevtodiyenko, Aleksey, Jones, Anthony, Muhunthan, Vishaka, Abdelhady, Gihad, Shackelford, David, Goun, Elena
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.06.2019; Nature Publishing Group
• Subjects: 631/1647/245/2222; 631/67/2321; 631/67/2327; 631/92/96; Absorption; Animals; Bioinformatics; Biological Microscopy; Biological Techniques; Biological Transport; Bioluminescence; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Disease control; Drug development; Drug metabolism; Emission; Female; Fluorodeoxyglucose F18 - metabolism; Glucose; Glucose - metabolism; Glucose transport; Glucose Transporter Type 1 - physiology; Humans; In vivo methods and tests; Life Sciences; Luciferases - metabolism; Medical imaging; Medical research; Medicine, Experimental; Metabolism; Metabolites; Mice, Knockout; Mice, Nude; Molecular probes; Neoplasms, Experimental - diagnostic imaging; Neoplasms, Experimental - metabolism; Neoplasms, Experimental - pathology; Positron emission tomography; Positron-Emission Tomography - methods; Proteomics; Radiopharmaceuticals - metabolism; Reagents; Testing; Tomography; Tracers; Tumor Cells, Cultured
• ISSN: 1548-7091; 1548-7105; 1548-7105
• DOI: 10.1038/s41592-019-0421-z

Glucose is a major source of energy for most living organisms, and its aberrant uptake is linked to many pathological conditions. However, our understanding of disease-associated glucose flux is limited owing to the lack of robust tools. To date, positron-emission tomography imaging remains the gold standard for measuring glucose uptake, and no optical tools exist for non-invasive longitudinal imaging of this important metabolite in in vivo settings. Here, we report the development of a bioluminescent glucose-uptake probe for real-time, non-invasive longitudinal imaging of glucose absorption both in vitro and in vivo. In addition, we demonstrate that the sensitivity of our method is comparable with that of commonly used 18 F-FDG-positron-emission-tomography tracers and validate the bioluminescent glucose-uptake probe as a tool for the identification of new glucose transport inhibitors. The new imaging reagent enables a wide range of applications in the fields of metabolism and drug development. A bioluminescent glucose-uptake probe enables accurate, real-time, non-invasive longitudinal imaging of d -glucose absorption both in vitro and in vivo.