Quantification of liver glucose metabolism by positron emission tomography: Validation study in pigs

Patricia Iozzo; Mikko J. Jarvisalo; Jan Kiss; Ronald Borra; Gratian A. Naum; Antti Viljanen; Tapio Viljanen; Amalia Gastaldelli; Emma Buzzigoli; Letizia Guiducci; Elisabetta Barsotti; Timo Savunen; Juhani Knuuti; Merja Haaparanta-Solin; Ele Ferrannini; Pirjo Nuutila

doi:10.1053/j.gastro.2006.12.040

Quantification of liver glucose metabolism by positron emission tomography: Validation study in pigs

Patricia Iozzo^*, Mikko J. Jarvisalo, Jan Kiss, Ronald Borra, Gratian A. Naum, Antti Viljanen, Tapio Viljanen, Amalia Gastaldelli, Emma Buzzigoli, Letizia Guiducci, Elisabetta Barsotti, Timo Savunen, Juhani Knuuti, Merja Haaparanta-Solin, Ele Ferrannini, Pirjo Nuutila

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

62 Citations (Scopus)

Abstract

Background & Aims: The liver is inaccessible to organ balance measurements in humans. To validate [F-18]fluorodeoxyglucose ([F-18]FDG) positron emission tomography (PET) in the quantification of hepatic glucose uptake (HGU), we determined [F-18]FDG modeling parameters, lumped constant (LC), and input functions (single arterial versus dual). Methods: Anesthetized pigs were studied during fasting (n = 6), physiologic (n = 4), and supraphysiologic (n = 4) hyperinsulinemia. PET was performed with (CO)-O-15 (blood pool) and [F-18]FDG (glucose uptake). 6,6-Deuterated glucose ([H-2]G) was coinjected with [F-18]FDG and blood collected from the carotid artery and portal and hepatic veins to compute LC as ratio between tracers fractional extraction. HGU was estimated from PET images and ex vivo from high-performance liquid chromatography measurements of liver [F-18]FDG versus [F-18]FDG-6-phosphate and [F-18]glycogen. Endogenous glucose production was measured with [H-2]G and hepatic blood flow by flowmeters. Results: HGU was increased in hyperinsulinemia versus fasting (P <.05). Fractional extraction of [F-18]FDG and [H-2]G was similar (not significant), intercorrelated (r = 0.98, P <.0001), and equally higher during hyperinsulinemia than fasting (P 0.95, P <.0001), with a modest underestimation of HGU by the former. Conclusions: [F-18]FDG-PET-derived parameters provide accurate quantification of HGU and estimates of liver perfusion and glucose production. In the liver, LC of [F-18]FDG is nearly unitary. Using a single arterial input introduces only a small error in estimation of HGU.

Original language	English
Pages (from-to)	531-542
Number of pages	12
Journal	Gastroenterology
Volume	132
Issue number	2
DOIs	https://doi.org/10.1053/j.gastro.2006.12.040
Publication status	Published - Feb-2007

Keywords

BRAIN TRANSFER CONSTANTS
TIME UPTAKE DATA
INSULIN-RESISTANCE
F-18 FLUORODEOXYGLUCOSE
LUMPED CONSTANT
GRAPHICAL EVALUATION
MODEL
HUMANS
MUSCLE
GLUCOKINASE

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Quantification of Liver Glucose Metabolism by Positron Emission Tomography
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Iozzo, P., Jarvisalo, M. J., Kiss, J., Borra, R., Naum, G. A., Viljanen, A., Viljanen, T., Gastaldelli, A., Buzzigoli, E., Guiducci, L., Barsotti, E., Savunen, T., Knuuti, J., Haaparanta-Solin, M., Ferrannini, E., & Nuutila, P. (2007). Quantification of liver glucose metabolism by positron emission tomography: Validation study in pigs. Gastroenterology, 132(2), 531-542. https://doi.org/10.1053/j.gastro.2006.12.040

@article{d7fb5e5d9f6c4432bc068bd0da3f7f34,

title = "Quantification of liver glucose metabolism by positron emission tomography: Validation study in pigs",

abstract = "Background & Aims: The liver is inaccessible to organ balance measurements in humans. To validate [F-18]fluorodeoxyglucose ([F-18]FDG) positron emission tomography (PET) in the quantification of hepatic glucose uptake (HGU), we determined [F-18]FDG modeling parameters, lumped constant (LC), and input functions (single arterial versus dual). Methods: Anesthetized pigs were studied during fasting (n = 6), physiologic (n = 4), and supraphysiologic (n = 4) hyperinsulinemia. PET was performed with (CO)-O-15 (blood pool) and [F-18]FDG (glucose uptake). 6,6-Deuterated glucose ([H-2]G) was coinjected with [F-18]FDG and blood collected from the carotid artery and portal and hepatic veins to compute LC as ratio between tracers fractional extraction. HGU was estimated from PET images and ex vivo from high-performance liquid chromatography measurements of liver [F-18]FDG versus [F-18]FDG-6-phosphate and [F-18]glycogen. Endogenous glucose production was measured with [H-2]G and hepatic blood flow by flowmeters. Results: HGU was increased in hyperinsulinemia versus fasting (P <.05). Fractional extraction of [F-18]FDG and [H-2]G was similar (not significant), intercorrelated (r = 0.98, P <.0001), and equally higher during hyperinsulinemia than fasting (P 0.95, P <.0001), with a modest underestimation of HGU by the former. Conclusions: [F-18]FDG-PET-derived parameters provide accurate quantification of HGU and estimates of liver perfusion and glucose production. In the liver, LC of [F-18]FDG is nearly unitary. Using a single arterial input introduces only a small error in estimation of HGU.",

keywords = "BRAIN TRANSFER CONSTANTS, TIME UPTAKE DATA, INSULIN-RESISTANCE, F-18 FLUORODEOXYGLUCOSE, LUMPED CONSTANT, GRAPHICAL EVALUATION, MODEL, HUMANS, MUSCLE, GLUCOKINASE",

author = "Patricia Iozzo and Jarvisalo, {Mikko J.} and Jan Kiss and Ronald Borra and Naum, {Gratian A.} and Antti Viljanen and Tapio Viljanen and Amalia Gastaldelli and Emma Buzzigoli and Letizia Guiducci and Elisabetta Barsotti and Timo Savunen and Juhani Knuuti and Merja Haaparanta-Solin and Ele Ferrannini and Pirjo Nuutila",

year = "2007",

month = feb,

doi = "10.1053/j.gastro.2006.12.040",

language = "English",

volume = "132",

pages = "531--542",

journal = "Gastroenterology",

issn = "0016-5085",

publisher = "W B SAUNDERS CO-ELSEVIER INC",

number = "2",

}

Iozzo, P, Jarvisalo, MJ, Kiss, J, Borra, R, Naum, GA, Viljanen, A, Viljanen, T, Gastaldelli, A, Buzzigoli, E, Guiducci, L, Barsotti, E, Savunen, T, Knuuti, J, Haaparanta-Solin, M, Ferrannini, E & Nuutila, P 2007, 'Quantification of liver glucose metabolism by positron emission tomography: Validation study in pigs', Gastroenterology, vol. 132, no. 2, pp. 531-542. https://doi.org/10.1053/j.gastro.2006.12.040

TY - JOUR

T1 - Quantification of liver glucose metabolism by positron emission tomography

T2 - Validation study in pigs

AU - Iozzo, Patricia

AU - Jarvisalo, Mikko J.

AU - Kiss, Jan

AU - Borra, Ronald

AU - Naum, Gratian A.

AU - Viljanen, Antti

AU - Viljanen, Tapio

AU - Gastaldelli, Amalia

AU - Buzzigoli, Emma

AU - Guiducci, Letizia

AU - Barsotti, Elisabetta

AU - Savunen, Timo

AU - Knuuti, Juhani

AU - Haaparanta-Solin, Merja

AU - Ferrannini, Ele

AU - Nuutila, Pirjo

PY - 2007/2

Y1 - 2007/2

N2 - Background & Aims: The liver is inaccessible to organ balance measurements in humans. To validate [F-18]fluorodeoxyglucose ([F-18]FDG) positron emission tomography (PET) in the quantification of hepatic glucose uptake (HGU), we determined [F-18]FDG modeling parameters, lumped constant (LC), and input functions (single arterial versus dual). Methods: Anesthetized pigs were studied during fasting (n = 6), physiologic (n = 4), and supraphysiologic (n = 4) hyperinsulinemia. PET was performed with (CO)-O-15 (blood pool) and [F-18]FDG (glucose uptake). 6,6-Deuterated glucose ([H-2]G) was coinjected with [F-18]FDG and blood collected from the carotid artery and portal and hepatic veins to compute LC as ratio between tracers fractional extraction. HGU was estimated from PET images and ex vivo from high-performance liquid chromatography measurements of liver [F-18]FDG versus [F-18]FDG-6-phosphate and [F-18]glycogen. Endogenous glucose production was measured with [H-2]G and hepatic blood flow by flowmeters. Results: HGU was increased in hyperinsulinemia versus fasting (P <.05). Fractional extraction of [F-18]FDG and [H-2]G was similar (not significant), intercorrelated (r = 0.98, P <.0001), and equally higher during hyperinsulinemia than fasting (P 0.95, P <.0001), with a modest underestimation of HGU by the former. Conclusions: [F-18]FDG-PET-derived parameters provide accurate quantification of HGU and estimates of liver perfusion and glucose production. In the liver, LC of [F-18]FDG is nearly unitary. Using a single arterial input introduces only a small error in estimation of HGU.

AB - Background & Aims: The liver is inaccessible to organ balance measurements in humans. To validate [F-18]fluorodeoxyglucose ([F-18]FDG) positron emission tomography (PET) in the quantification of hepatic glucose uptake (HGU), we determined [F-18]FDG modeling parameters, lumped constant (LC), and input functions (single arterial versus dual). Methods: Anesthetized pigs were studied during fasting (n = 6), physiologic (n = 4), and supraphysiologic (n = 4) hyperinsulinemia. PET was performed with (CO)-O-15 (blood pool) and [F-18]FDG (glucose uptake). 6,6-Deuterated glucose ([H-2]G) was coinjected with [F-18]FDG and blood collected from the carotid artery and portal and hepatic veins to compute LC as ratio between tracers fractional extraction. HGU was estimated from PET images and ex vivo from high-performance liquid chromatography measurements of liver [F-18]FDG versus [F-18]FDG-6-phosphate and [F-18]glycogen. Endogenous glucose production was measured with [H-2]G and hepatic blood flow by flowmeters. Results: HGU was increased in hyperinsulinemia versus fasting (P <.05). Fractional extraction of [F-18]FDG and [H-2]G was similar (not significant), intercorrelated (r = 0.98, P <.0001), and equally higher during hyperinsulinemia than fasting (P 0.95, P <.0001), with a modest underestimation of HGU by the former. Conclusions: [F-18]FDG-PET-derived parameters provide accurate quantification of HGU and estimates of liver perfusion and glucose production. In the liver, LC of [F-18]FDG is nearly unitary. Using a single arterial input introduces only a small error in estimation of HGU.

KW - BRAIN TRANSFER CONSTANTS

KW - TIME UPTAKE DATA

KW - INSULIN-RESISTANCE

KW - F-18 FLUORODEOXYGLUCOSE

KW - LUMPED CONSTANT

KW - GRAPHICAL EVALUATION

KW - MODEL

KW - HUMANS

KW - MUSCLE

KW - GLUCOKINASE

U2 - 10.1053/j.gastro.2006.12.040

DO - 10.1053/j.gastro.2006.12.040

M3 - Article

SN - 0016-5085

VL - 132

SP - 531

EP - 542

JO - Gastroenterology

JF - Gastroenterology

IS - 2

ER -

Quantification of liver glucose metabolism by positron emission tomography: Validation study in pigs

Abstract

Keywords

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