Effect of starvation on brain glucose metabolism and 18F-2-fluoro-2-deoxyglucose uptake: an experimental in-vivo and ex-vivo study
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...
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SpringerOpen
2018-06-01
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Series: | EJNMMI Research |
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Online Access: | http://link.springer.com/article/10.1186/s13550-018-0398-0 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 Sambuceti Cecilia Marini |
spellingShingle |
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 Sambuceti Cecilia Marini Effect of starvation on brain glucose metabolism and 18F-2-fluoro-2-deoxyglucose uptake: an experimental in-vivo and ex-vivo study EJNMMI Research Brain metabolism PET/CT imaging FDG Starvation Neuroimaging |
author_facet |
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 Sambuceti Cecilia Marini |
author_sort |
Ambra Buschiazzo |
title |
Effect of starvation on brain glucose metabolism and 18F-2-fluoro-2-deoxyglucose uptake: an experimental in-vivo and ex-vivo study |
title_short |
Effect of starvation on brain glucose metabolism and 18F-2-fluoro-2-deoxyglucose uptake: an experimental in-vivo and ex-vivo study |
title_full |
Effect of starvation on brain glucose metabolism and 18F-2-fluoro-2-deoxyglucose uptake: an experimental in-vivo and ex-vivo study |
title_fullStr |
Effect of starvation on brain glucose metabolism and 18F-2-fluoro-2-deoxyglucose uptake: an experimental in-vivo and ex-vivo study |
title_full_unstemmed |
Effect of starvation on brain glucose metabolism and 18F-2-fluoro-2-deoxyglucose uptake: an experimental in-vivo and ex-vivo study |
title_sort |
effect of starvation on brain glucose metabolism and 18f-2-fluoro-2-deoxyglucose uptake: an experimental in-vivo and ex-vivo study |
publisher |
SpringerOpen |
series |
EJNMMI Research |
issn |
2191-219X |
publishDate |
2018-06-01 |
description |
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. |
topic |
Brain metabolism PET/CT imaging FDG Starvation Neuroimaging |
url |
http://link.springer.com/article/10.1186/s13550-018-0398-0 |
work_keys_str_mv |
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doaj-876039e219eb417883e69580978533522020-11-24T20:44:10ZengSpringerOpenEJNMMI Research2191-219X2018-06-018111210.1186/s13550-018-0398-0Effect of starvation on brain glucose metabolism and 18F-2-fluoro-2-deoxyglucose uptake: an experimental in-vivo and ex-vivo studyAmbra Buschiazzo0Vanessa Cossu1Matteo Bauckneht2Annamaria Orengo3Patrizia Piccioli4Laura Emionite5Giovanna Bianchi6Federica Grillo7Anna Rocchi8Francesco Di Giulio9Francesco Fiz10Lizzia Raffaghello11Flavio Nobili12Silvia Bruno13Giacomo Caviglia14Silvia Ravera15Fabio Benfenati16Michele Piana17Silvia Morbelli18Gianmario Sambuceti19Cecilia Marini20Department of Health Science, Nuclear Medicine Unit, University of GenoaNuclear Medicine Unit, Polyclinic San Martino HospitalDepartment of Health Science, Nuclear Medicine Unit, University of GenoaNuclear Medicine Unit, Polyclinic San Martino HospitalCell Biology Unit, Polyclinic San Martino HospitalAnimal Facility, Polyclinic San Martino HospitalOncology Lab, IRCCS Giannina GasliniPathology, Department of Integrated Surgical and Diagnosic Sciences (DISC), University of GenoaCenter for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia (IIT)Nuclear Medicine Unit, Polyclinic San Martino HospitalDepartment of Health Science, Nuclear Medicine Unit, University of GenoaOncology Lab, IRCCS Giannina GasliniClinical Neurology, Polyclinic San Martino HospitalDepartment of Experimental Medicine, University of GenoaDepartment of Mathematics (DIMA), University of GenoaDepartment of Pharmacy, Biochemistry Laboratory, University of GenoaCenter for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia (IIT)Department of Mathematics (DIMA), University of GenoaDepartment of Health Science, Nuclear Medicine Unit, University of GenoaDepartment of Health Science, Nuclear Medicine Unit, University of GenoaNuclear Medicine Unit, Polyclinic San Martino HospitalAbstract 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.http://link.springer.com/article/10.1186/s13550-018-0398-0Brain metabolismPET/CT imagingFDGStarvationNeuroimaging |