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Feasibility of direct mapping of cerebral fluorodeoxy-D-glucose metabolism in situ at subcellular resolution using soft X-ray fluorescence

DOI: 10.1002/jnr.23171 DOI Help

Authors: Arne Schousboe , Mary C. Mckenna , Carole Poitry - Yamate (Ecole polytechnique Federale de Lausanne) , Alessandra Gianoncelli (ELETTRA) , Burkhard Kaulich (ELETTRA; Diamond Light Source) , George Kourousias (ELETTRA) , Arthur W. Magill (Ecole Polytechnique Fédérale de Lausanne (EPFL)) , Mario Lepore (Ecole Polytechnique Fédérale de Lausanne (EPFL)) , Vincent Gajdosik (Bern University Hospital) , Rolf Gruetter (Ecole Polytechnique Fédérale de Lausanne (EPFL))
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Neuroscience Research , VOL 91 (8) , PAGES 1050 - 1058

State: Published (Approved)
Published: August 2013

Abstract: Glucose metabolism is difficult to image with cellular resolution in mammalian brain tissue, particularly with 18fluorodeoxy-D-glucose (FDG) positron emission tomography (PET). To this end, we explored the potential of synchrotron-based low-energy X-ray fluorescence (LEXRF) to image the stable isotope of fluorine (F) in phosphorylated FDG (DG-6P) at 1 μm2 spatial resolution in 3-μm-thick brain slices. The excitation-dependent fluorescence F signal at 676 eV varied linearly with FDG concentration between 0.5 and 10 mM, whereas the endogenous background F signal was undetectable in brain. To validate LEXRF mapping of fluorine, FDG was administered in vitro and in vivo, and the fluorine LEXRF signal from intracellular trapped FDG-6P over selected brain areas rich in radial glia was spectrally quantitated at 1 μm2 resolution. The subsequent generation of spatial LEXRF maps of F reproduced the expected localization and gradients of glucose metabolism in retinal Müller glia. In addition, FDG uptake was localized to periventricular hypothalamic tanycytes, whose morphological features were imaged simultaneously by X-ray absorption. We conclude that the high specificity of photon emission from F and its spatial mapping at ≤1 μm resolution demonstrates the ability to identify glucose uptake at subcellular resolution and holds remarkable potential for imaging glucose metabolism in biological tissue

Journal Keywords: Fluorodeoxy-D-glucose; low-energy X-ray fluorescence spectromicroscopy; periventricular hypothalamus; radial glia; retina; synchrotron; Free Electron Lasers

Subject Areas: Biology and Bio-materials

Facility: ELETTRA

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