In vivo imaging of epileptic activity using 2-NBDG, a fluorescent deoxyglucose analog

Tsytsarev, Vassiliy; Maslov, Konstantin; Yao, Junjie; Parameswar, Archana R.; Demchenko, Alexei V.; Wang, Lihong V.

doi:10.1016/j.jneumeth.2011.09.005

Cited by 55 publications

(37 citation statements)

References 37 publications

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“…2-NBDG is a newly developed fluorescent 2-deoxyglucose (2-DG) analog (Bem et al, 2007; Cheng et al, 2006; Gaudreault et al, 2008; Itoh et al, 2004; Langsner et al, 2011; Millon et al, 2011; O’Neil et al, 2005; Sheth et al, 2009; Tsytsarev et al, 2012). Like the FDG (molecular weight: 181) used in PET studies, 2-NBDG is transported into cells via the same GLUT as glucose (Sheth et al, 2009).…”

Section: Methodsmentioning

confidence: 99%

Noninvasive photoacoustic computed tomography of mouse brain metabolism in vivo

et al. 2013

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We have demonstrated the feasibility of imaging mouse brain metabolism using photoacoustic computed tomography (PACT), a fast, noninvasive and functional imaging modality with optical contrast and acoustic resolution. Brain responses to forepaw stimulations were imaged transdermally and transcranially. 2-NBDG, which diffuses well across the blood-brain-barrier, provided exogenous contrast for photoacoustic imaging of glucose response. Concurrently, hemoglobin provided endogenous contrast for photoacoustic imaging of hemodynamic response. Glucose and hemodynamic responses were quantitatively decoupled by using two-wavelength measurements. We found that glucose uptake and blood perfusion around the somatosensory region of the contralateral hemisphere were both increased by stimulations, indicating elevated neuron activity. While the glucose response area was more homogenous and confined within the somatosensory region, the hemodynamic response area had a clear vascular pattern and spread wider than the somatosensory region. Our results demonstrate that 2-NBDG-enhanced PACT is a promising tool for noninvasive studies of brain metabolism.

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Section: Methodsmentioning

confidence: 99%

Noninvasive photoacoustic computed tomography of mouse brain metabolism in vivo

et al. 2013

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“…Prior work has shown that 2-NBDG enters a cell via glucose transporters and is phosphorylated at the C-6 position by hexokinases I-II. The phosphorylated fluorescent metabolite, 2-NBDG-6-phosphate, remains in the cell until decomposition into a nonfluorescent form (9)(10)(11)(12)(13). Compared with nonmalignant cells, 2-NBDG is rapidly taken up by malignant cells, providing an optical marker for detection of malignant cells.…”

Section: Resultsmentioning

confidence: 99%

High-throughput screening of rare metabolically active tumor cells in pleural effusion and peripheral blood of lung cancer patients

Tang

Wang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Malignant pleural effusion (MPE), the presence of malignant cells in pleural fluid, is often the first sign of many cancers and occurs in patients with metastatic malignancies. Accurate detection of tumor cells in pleural fluid is crucial because the presence of MPE denotes an advanced stage of disease and directs a switch in clinical managements. Cytology, as a traditional diagnostic tool, has limited sensitivity especially when tumor cells are not abundant, and may be confounded by reactive mesothelial cells in the pleural fluid. We describe a highly sensitive approach for rapid detection of metabolically active tumor cells in MPE via exploiting the altered glucose metabolism of tumor cells relative to benign cells. Metabolically active tumor cells with high glucose uptake, as evaluated by a fluorescent glucose analog (2-NBDG), are identified by high-throughput fluorescence screening within a chip containing 200,000 addressable microwells and collected for malignancy confirmation via single-cell sequencing. We demonstrate the utility of this approach through analyzing MPE from a cohort of lung cancer patients. Most candidate tumor cells identified are confirmed to harbor the same driver oncogenes as their primary lesions. In some patients, emergence of secondary mutations that mediate acquired resistance to ongoing targeted therapies is also detected before resistance is manifested in the clinical imaging. The detection scheme can be extended to analyze peripheral blood samples. Our approach may serve as a valuable complement to cytology in MPE diagnosis, helping identify the driver oncogenes and resistance-leading mutations for targeted therapies.

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“…Therefore, the distribution of these glucose substitutes is a good reflection of metabolic activity [14, 15, 67]. A fluorescent glucose substitute, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG), was successfully used for visualization of neural activity in vitro as well as in vivo [64, 67]. In experimental and clinical practice, a radioactive beam limits the usage of the radioactive labeled 2-DG analog.…”

Section: Metabolic-related Optical Imagingmentioning

confidence: 99%

“…In the study, performed with participation of one of the authors [64, 67], 2-NBDG was employed for visualization of in vivo epileptic activities induced by intracortical injection of 4-aminopyridine (4-AP), which is a common potassium-channel inhibitor that causes epileptic activity. The increased uptake rate of 2-NBDG at the injection site of 4-AP reflected increased cortical metabolism caused by epileptic seizures and produced a fluorescent signal in this site.…”

Section: Metabolic-related Optical Imagingmentioning

confidence: 99%

Living Brain Optical Imaging: Technology, Methods and Applications

Tsytsarev

Bernardelli

Maslov

2012

J Neurosci Neuroengng

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Within the last few decades, optical imaging methods have yielded revolutionary results when applied to all parts of the central nervous system. The purpose of this review is to analyze research possibilities and limitations of several novel imaging techniques and show some of the most interesting achievements obtained by these methods. Here we covered intrinsic optical imaging, voltage-sensitive dye, photoacoustic, optical coherence tomography, near-infrared spectroscopy and some other techniques. All of them are mainly applicable for experimental neuroscience but some of them also suitable for the clinical studies.

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In vivo imaging of epileptic activity using 2-NBDG, a fluorescent deoxyglucose analog

Cited by 55 publications

References 37 publications

Noninvasive photoacoustic computed tomography of mouse brain metabolism in vivo

Noninvasive photoacoustic computed tomography of mouse brain metabolism in vivo

High-throughput screening of rare metabolically active tumor cells in pleural effusion and peripheral blood of lung cancer patients

Living Brain Optical Imaging: Technology, Methods and Applications

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