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

5 Citations (Scopus)

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

Fingerprint

Fluorodeoxyglucose F18
Starvation
Glucose
Brain
Deoxyglucose
Skeletal Muscle
Food Deprivation
Hexokinase
Neurodegenerative Diseases
Fasting
Theoretical Models
Phosphorylation
Food
Control Groups
Water

Keywords

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

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Effect of starvation on brain glucose metabolism and 18F-2-fluoro-2-deoxyglucose uptake : an experimental in-vivo and ex-vivo study. / Buschiazzo, Ambra; Cossu, Vanessa; Bauckneht, Matteo; Orengo, Annamaria; Piccioli, Patrizia; Emionite, Laura; Bianchi, Giovanna; Grillo, Federica; Rocchi, Anna; Di Giulio, Francesco; Fiz, Francesco; Raffaghello, Lizzia; Nobili, Flavio; Bruno, Silvia; Caviglia, Giacomo; Ravera, Silvia; Benfenati, Fabio; Piana, Michele; Morbelli, Silvia; Sambuceti, Gianmario; Marini, Cecilia.

In: EJNMMI Research, Vol. 8, 44, 01.01.2018.

Research output: Contribution to journalArticle

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, Sambuceti, G & 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, vol. 8, 44. https://doi.org/10.1186/s13550-018-0398-0
Buschiazzo, Ambra ; Cossu, Vanessa ; Bauckneht, Matteo ; Orengo, Annamaria ; Piccioli, Patrizia ; Emionite, Laura ; Bianchi, Giovanna ; Grillo, Federica ; Rocchi, Anna ; Di Giulio, Francesco ; Fiz, Francesco ; Raffaghello, Lizzia ; Nobili, Flavio ; Bruno, Silvia ; Caviglia, Giacomo ; Ravera, Silvia ; Benfenati, Fabio ; Piana, Michele ; Morbelli, Silvia ; Sambuceti, Gianmario ; Marini, Cecilia. / Effect of starvation on brain glucose metabolism and 18F-2-fluoro-2-deoxyglucose uptake : an experimental in-vivo and ex-vivo study. In: EJNMMI Research. 2018 ; Vol. 8.
@article{9992db700ed546e3bb5e562dea7cb959,
title = "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 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.",
keywords = "Brain metabolism, FDG, Neuroimaging, PET/CT imaging, Starvation",
author = "Ambra Buschiazzo and Vanessa Cossu and Matteo Bauckneht and Annamaria Orengo and Patrizia Piccioli and Laura Emionite and Giovanna Bianchi and Federica Grillo and Anna Rocchi and {Di Giulio}, Francesco and Francesco Fiz and Lizzia Raffaghello and Flavio Nobili and Silvia Bruno and Giacomo Caviglia and Silvia Ravera and Fabio Benfenati and Michele Piana and Silvia Morbelli and Gianmario Sambuceti and Cecilia Marini",
year = "2018",
month = "1",
day = "1",
doi = "10.1186/s13550-018-0398-0",
language = "English",
volume = "8",
journal = "EJNMMI Research",
issn = "2191-219X",
publisher = "Springer Berlin",

}

TY - JOUR

T1 - Effect of starvation on brain glucose metabolism and 18F-2-fluoro-2-deoxyglucose uptake

T2 - an experimental in-vivo and ex-vivo study

AU - Buschiazzo, Ambra

AU - Cossu, Vanessa

AU - Bauckneht, Matteo

AU - Orengo, Annamaria

AU - Piccioli, Patrizia

AU - Emionite, Laura

AU - Bianchi, Giovanna

AU - Grillo, Federica

AU - Rocchi, Anna

AU - Di Giulio, Francesco

AU - Fiz, Francesco

AU - Raffaghello, Lizzia

AU - Nobili, Flavio

AU - Bruno, Silvia

AU - Caviglia, Giacomo

AU - Ravera, Silvia

AU - Benfenati, Fabio

AU - Piana, Michele

AU - Morbelli, Silvia

AU - Sambuceti, Gianmario

AU - Marini, Cecilia

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Brain metabolism

KW - FDG

KW - Neuroimaging

KW - PET/CT imaging

KW - Starvation

UR - http://www.scopus.com/inward/record.url?scp=85048319542&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048319542&partnerID=8YFLogxK

U2 - 10.1186/s13550-018-0398-0

DO - 10.1186/s13550-018-0398-0

M3 - Article

AN - SCOPUS:85048319542

VL - 8

JO - EJNMMI Research

JF - EJNMMI Research

SN - 2191-219X

M1 - 44

ER -