Effect of starvation on brain glucose metabolism and 18F-2-fluoro-2-deoxyglucose uptake: an experimental in-vivo and ex-vivo study

Ambra Buschiazzo, Vanessa Cossu, Matteo Bauckneht, Annamaria Orengo, Patrizia Piccioli, Laura Emionite, Giovanna Bianchi, Federica Grillo, Anna Rocchi, Francesco Di Giulio, Francesco Fiz, Lizzia Raffaghello, Flavio Nobili, Silvia Bruno, Giacomo Caviglia, Silvia Ravera, Fabio Benfenati, Michele Piana, Silvia Morbelli, Gianmario SambucetiCecilia Marini

Research output: Contribution to journalArticle

Abstract

Background: The close connection between neuronal activity and glucose consumption accounts for the clinical value of 18F-fluoro-2-deoxyglucose (FDG) imaging in neurodegenerative disorders. Nevertheless, brain metabolic response to starvation (STS) might hamper the diagnostic accuracy of FDG PET/CT when the cognitive impairment results in a severe food deprivation. Methods: Thirty six-week-old BALB/c female mice were divided into two groups: “control” group (n = 15) were kept under standard conditions and exposed to fasting for 6 h before the study; the remaining “STS” mice were submitted to 48 h STS (absence of food and free access to water) before imaging. In each group, nine mice were submitted to dynamic micro-PET imaging to estimate brain and skeletal muscle glucose consumption (C- and SM-MRGlu*) by Patlak approach, while six mice were sacrificed for ex vivo determination of the lumped constant, defined as the ratio between CMRGlu* and glucose consumption measured by glucose removal from the incubation medium (n = 3) or biochemical analyses (n = 3), respectively. Results: CMRGlu* was lower in starved than in control mice (46.1 ± 23.3 vs 119.5 ± 40.2 nmol × min−1 × g−1, respectively, p < 0.001). Ex vivo evaluation documented a remarkable stability of lumped constant as documented by the stability of GLUT expression, G6Pase activity, and kinetic features of hexokinase-catalyzed phosphorylation. However, brain SUV in STS mice was even (though not significantly) higher with respect to control mice. Conversely, a marked decrease in both SM-MRGlu* and SM-SUV was documented in STS mice with respect to controls. Conclusions: STS markedly decreases brain glucose consumption without altering measured FDG SUV in mouse experimental models. This apparent paradox does not reflect any change in lumped constant. Rather, it might be explained by the metabolic response of the whole body: the decrease in FDG sequestration by the skeletal muscle is as profound as to prolong tracer persistence in the bloodstream and thus its availability for brain uptake.

Original languageEnglish
Article number44
JournalEJNMMI Research
Volume8
DOIs
Publication statusPublished - Jan 1 2018

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Keywords

  • Brain metabolism
  • FDG
  • Neuroimaging
  • PET/CT imaging
  • Starvation

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Buschiazzo, A., Cossu, V., Bauckneht, M., Orengo, A., Piccioli, P., Emionite, L., Bianchi, G., Grillo, F., Rocchi, A., Di Giulio, F., Fiz, F., Raffaghello, L., Nobili, F., Bruno, S., Caviglia, G., Ravera, S., Benfenati, F., Piana, M., Morbelli, S., ... Marini, C. (2018). Effect of starvation on brain glucose metabolism and 18F-2-fluoro-2-deoxyglucose uptake: an experimental in-vivo and ex-vivo study. EJNMMI Research, 8, [44]. https://doi.org/10.1186/s13550-018-0398-0