Glucose metabolism in human malignant gliomas measured quantitatively with PET, 1-[C-11]glucose and FDG: Analysis of the FDG lumped constant

Alexander M. Spence; Mark Muzi; Michael M. Graham; Finbarr O'Sullivan; Kenneth A. Krohn; Jeanne M. Link; Thomas K. Lewellen; Barbara Lewellen; Scott D. Freeman; Mitchel S. Berger; George A. Ojemann

Glucose metabolism in human malignant gliomas measured quantitatively with PET, 1-[C-11]glucose and FDG: Analysis of the FDG lumped constant

Alexander M. Spence, Mark Muzi, Michael M. Graham, Finbarr O'Sullivan, Kenneth A. Krohn, Jeanne M. Link, Thomas K. Lewellen, Barbara Lewellen, Scott D. Freeman, Mitchel S. Berger, George A. Ojemann

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125 Scopus citations

Abstract

Calculation of the glucose metabolic rate (MRGlc) brain with PET and 2- [¹⁸F]fluoro-2-deoxy-D-glucose (FDG) requires knowing the rate of uptake of FDG relative to glucose from plasma into metabolite pools in the tissue. The proportionality factor for this is the FDG lumped constant (LC(FDG)), the ratio of the volumes of distribution of FDG and glucose multiplied by the hexokinase phosphorylation ratio for the two hexoses, KM(Glc)·Vm(FDG)/Km(FDG)·Vm(Glc). MRGlc equals the FDG metabolic rate (MRFDG) divided by the LC(FDG), i.e., MRGlc = MRFDG/LC(FDG) and LC(FDG) = MRFDG/MRGlc. This investigation tested the hypothesis that LC(FDG) is significantly higher in gliomas than it is in brain uninvolved with tumor. Methods: We imaged 40 patients with malignant gliomas with 1-[¹¹C]glucose followed by FDG. The metabolic rates MRGlc and MRFDG were estimated for glioma and contralateral brain regions of interest by an optimization program based on three-compartment, four-rate constant models for the two hexoses. Results: The LC(FDG), estimated as MRFDG/MRGlc, in gliomas was 1.40 ± 0.46 (mean ± s.d.; range = 0.72-3.10), whereas in non-tumor-bearing contralateral brain, it was 0.86 ± 0.14 (range = 0.61-1.21) (p < 0.001, glioma versus contralateral brain). Conclusion: These data strongly suggest that the glioma LC(FDG) exceeds that of contralateral brain, that quantitation of the glioma MRGlc with FDG requires knowing the LC(FDG) specific for the glioma and that the LC(FDG) of normal brain is higher than previously reported estimates of about 0.50. 2-Fluoro-2-deoxy-D-glucose/PET studies in which glioma glucose metabolism is calculated by the autoradiographic approach with normal brain rate constants and LC(FDG) will overestimate glioma MRGlc, to the extent that the glioma LC(FDG) exceeds the normal brain LC(FDG). 'Hot spots' visualized in FDG/PET studies of gliomas represent regions where MRGlc, LC(FDG) or their product is higher in glioma than it is in uninvolved brain tissue.

Original language	English (US)
Pages (from-to)	440-448
Number of pages	9
Journal	Journal of Nuclear Medicine
Volume	39
Issue number	3
State	Published - Mar 1998
Externally published	Yes

Keywords

Brain neoplasm
Glioma
Glucose metabolism
Lumped constant
PET

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging

Cite this

@article{622ebe5c33024239976dff38e635afa9,

title = "Glucose metabolism in human malignant gliomas measured quantitatively with PET, 1-[C-11]glucose and FDG: Analysis of the FDG lumped constant",

abstract = "Calculation of the glucose metabolic rate (MRGlc) brain with PET and 2- [18F]fluoro-2-deoxy-D-glucose (FDG) requires knowing the rate of uptake of FDG relative to glucose from plasma into metabolite pools in the tissue. The proportionality factor for this is the FDG lumped constant (LC(FDG)), the ratio of the volumes of distribution of FDG and glucose multiplied by the hexokinase phosphorylation ratio for the two hexoses, KM(Glc)·Vm(FDG)/Km(FDG)·Vm(Glc). MRGlc equals the FDG metabolic rate (MRFDG) divided by the LC(FDG), i.e., MRGlc = MRFDG/LC(FDG) and LC(FDG) = MRFDG/MRGlc. This investigation tested the hypothesis that LC(FDG) is significantly higher in gliomas than it is in brain uninvolved with tumor. Methods: We imaged 40 patients with malignant gliomas with 1-[11C]glucose followed by FDG. The metabolic rates MRGlc and MRFDG were estimated for glioma and contralateral brain regions of interest by an optimization program based on three-compartment, four-rate constant models for the two hexoses. Results: The LC(FDG), estimated as MRFDG/MRGlc, in gliomas was 1.40 ± 0.46 (mean ± s.d.; range = 0.72-3.10), whereas in non-tumor-bearing contralateral brain, it was 0.86 ± 0.14 (range = 0.61-1.21) (p < 0.001, glioma versus contralateral brain). Conclusion: These data strongly suggest that the glioma LC(FDG) exceeds that of contralateral brain, that quantitation of the glioma MRGlc with FDG requires knowing the LC(FDG) specific for the glioma and that the LC(FDG) of normal brain is higher than previously reported estimates of about 0.50. 2-Fluoro-2-deoxy-D-glucose/PET studies in which glioma glucose metabolism is calculated by the autoradiographic approach with normal brain rate constants and LC(FDG) will overestimate glioma MRGlc, to the extent that the glioma LC(FDG) exceeds the normal brain LC(FDG). 'Hot spots' visualized in FDG/PET studies of gliomas represent regions where MRGlc, LC(FDG) or their product is higher in glioma than it is in uninvolved brain tissue.",

keywords = "Brain neoplasm, Glioma, Glucose metabolism, Lumped constant, PET",

author = "Spence, {Alexander M.} and Mark Muzi and Graham, {Michael M.} and Finbarr O'Sullivan and Krohn, {Kenneth A.} and Link, {Jeanne M.} and Lewellen, {Thomas K.} and Barbara Lewellen and Freeman, {Scott D.} and Berger, {Mitchel S.} and Ojemann, {George A.}",

year = "1998",

month = mar,

language = "English (US)",

volume = "39",

pages = "440--448",

journal = "Journal of Nuclear Medicine",

issn = "0161-5505",

publisher = "Society of Nuclear Medicine Inc.",

number = "3",

}

TY - JOUR

T1 - Glucose metabolism in human malignant gliomas measured quantitatively with PET, 1-[C-11]glucose and FDG

T2 - Analysis of the FDG lumped constant

AU - Spence, Alexander M.

AU - Muzi, Mark

AU - Graham, Michael M.

AU - O'Sullivan, Finbarr

AU - Krohn, Kenneth A.

AU - Link, Jeanne M.

AU - Lewellen, Thomas K.

AU - Lewellen, Barbara

AU - Freeman, Scott D.

AU - Berger, Mitchel S.

AU - Ojemann, George A.

PY - 1998/3

Y1 - 1998/3

N2 - Calculation of the glucose metabolic rate (MRGlc) brain with PET and 2- [18F]fluoro-2-deoxy-D-glucose (FDG) requires knowing the rate of uptake of FDG relative to glucose from plasma into metabolite pools in the tissue. The proportionality factor for this is the FDG lumped constant (LC(FDG)), the ratio of the volumes of distribution of FDG and glucose multiplied by the hexokinase phosphorylation ratio for the two hexoses, KM(Glc)·Vm(FDG)/Km(FDG)·Vm(Glc). MRGlc equals the FDG metabolic rate (MRFDG) divided by the LC(FDG), i.e., MRGlc = MRFDG/LC(FDG) and LC(FDG) = MRFDG/MRGlc. This investigation tested the hypothesis that LC(FDG) is significantly higher in gliomas than it is in brain uninvolved with tumor. Methods: We imaged 40 patients with malignant gliomas with 1-[11C]glucose followed by FDG. The metabolic rates MRGlc and MRFDG were estimated for glioma and contralateral brain regions of interest by an optimization program based on three-compartment, four-rate constant models for the two hexoses. Results: The LC(FDG), estimated as MRFDG/MRGlc, in gliomas was 1.40 ± 0.46 (mean ± s.d.; range = 0.72-3.10), whereas in non-tumor-bearing contralateral brain, it was 0.86 ± 0.14 (range = 0.61-1.21) (p < 0.001, glioma versus contralateral brain). Conclusion: These data strongly suggest that the glioma LC(FDG) exceeds that of contralateral brain, that quantitation of the glioma MRGlc with FDG requires knowing the LC(FDG) specific for the glioma and that the LC(FDG) of normal brain is higher than previously reported estimates of about 0.50. 2-Fluoro-2-deoxy-D-glucose/PET studies in which glioma glucose metabolism is calculated by the autoradiographic approach with normal brain rate constants and LC(FDG) will overestimate glioma MRGlc, to the extent that the glioma LC(FDG) exceeds the normal brain LC(FDG). 'Hot spots' visualized in FDG/PET studies of gliomas represent regions where MRGlc, LC(FDG) or their product is higher in glioma than it is in uninvolved brain tissue.

AB - Calculation of the glucose metabolic rate (MRGlc) brain with PET and 2- [18F]fluoro-2-deoxy-D-glucose (FDG) requires knowing the rate of uptake of FDG relative to glucose from plasma into metabolite pools in the tissue. The proportionality factor for this is the FDG lumped constant (LC(FDG)), the ratio of the volumes of distribution of FDG and glucose multiplied by the hexokinase phosphorylation ratio for the two hexoses, KM(Glc)·Vm(FDG)/Km(FDG)·Vm(Glc). MRGlc equals the FDG metabolic rate (MRFDG) divided by the LC(FDG), i.e., MRGlc = MRFDG/LC(FDG) and LC(FDG) = MRFDG/MRGlc. This investigation tested the hypothesis that LC(FDG) is significantly higher in gliomas than it is in brain uninvolved with tumor. Methods: We imaged 40 patients with malignant gliomas with 1-[11C]glucose followed by FDG. The metabolic rates MRGlc and MRFDG were estimated for glioma and contralateral brain regions of interest by an optimization program based on three-compartment, four-rate constant models for the two hexoses. Results: The LC(FDG), estimated as MRFDG/MRGlc, in gliomas was 1.40 ± 0.46 (mean ± s.d.; range = 0.72-3.10), whereas in non-tumor-bearing contralateral brain, it was 0.86 ± 0.14 (range = 0.61-1.21) (p < 0.001, glioma versus contralateral brain). Conclusion: These data strongly suggest that the glioma LC(FDG) exceeds that of contralateral brain, that quantitation of the glioma MRGlc with FDG requires knowing the LC(FDG) specific for the glioma and that the LC(FDG) of normal brain is higher than previously reported estimates of about 0.50. 2-Fluoro-2-deoxy-D-glucose/PET studies in which glioma glucose metabolism is calculated by the autoradiographic approach with normal brain rate constants and LC(FDG) will overestimate glioma MRGlc, to the extent that the glioma LC(FDG) exceeds the normal brain LC(FDG). 'Hot spots' visualized in FDG/PET studies of gliomas represent regions where MRGlc, LC(FDG) or their product is higher in glioma than it is in uninvolved brain tissue.

KW - Brain neoplasm

KW - Glioma

KW - Glucose metabolism

KW - Lumped constant

KW - PET

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UR - http://www.scopus.com/inward/citedby.url?scp=0031930393&partnerID=8YFLogxK

M3 - Article

C2 - 9529289

AN - SCOPUS:0031930393

SN - 0161-5505

VL - 39

SP - 440

EP - 448

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

IS - 3

ER -

Glucose metabolism in human malignant gliomas measured quantitatively with PET, 1-[C-11]glucose and FDG: Analysis of the FDG lumped constant

Abstract

Keywords

ASJC Scopus subject areas

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