Direct mapping of F-19 in (19)FDG-6P in brain tissue at subcellular resolution using soft X-ray fluorescence
Low energy x-ray fluorescence (LEXRF) detection was optimized for imaging cerebral glucose metabolism by mapping the fluorine LEXRF signal of F-19 in (19)FDG, trapped as intracellular F-19-deoxyglucose-6-phosphate ((19)FDG-6P) at 1 mu m spatial resolution from 3 mu m thick brain slices. (19)FDG metabolism was evaluated in brain structures closely resembling the general cerebral cytoarchitecture following formalin fixation of brain slices and their inclusion in an epon matrix. 2-dimensional distribution maps of (19)FDG-6P were placed in a cytoarchitectural and morphological context by simultaneous LEXRF mapping of N and O, and scanning transmission x-ray (STXM) imaging. A disproportionately high uptake and metabolism of glucose was found in neuropil relative to intracellular domains of the cell body of hypothalamic neurons, showing directly that neurons, like glial cells, also metabolize glucose. As F-19-deoxyglucose-6P is structurally identical to F-18-deoxyglucose-6P, LEXRF of subcellular F-19 provides a link to in vivo (18)FDG PET, forming a novel basis for understanding the physiological mechanisms underlying the (18)FDG PET image, and the contribution of neurons and glia to the PET signal.