Absolute quantification of regional cerebral glucose utilization in mice by 18F-FDG small animal PET scanning and 2-14C-DG autoradiography

Hiroshi Toyama, Masanori Ichise, Jeih San Liow, Kendra J. Modell, Douglass C. Vines, Takanori Esaki, Michelle Cook, Jurgen Seidel, Louis Sokoloff, Michael V. Green, Robert B. Innis

Research output: Contribution to journal › Article

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Abstract

The purpose of this study was to evaluate the feasibility of absolute quantification of regional cerebral glucose utilization (rCMRglc) in mice by use of 18F-FDG and a small animal PET scanner. rCMR glc determined with 18F-FDG PET was compared with values determined simultaneously by the autoradiographic 2-14C-DG method. In addition, we compared the rCMRglc values under isoflurane, ketamine and xylazine anesthesia, and awake states. Methods: Immediately after injection of 18F-FDG and 2-14C-DG into mice, timed arterial samples were drawn over 45 min to determine the time courses of 18F-FDG and 2-14C-DG. Animals were euthanized at 45 min and their brain was imaged with the PET scanner. The brains were then processed for 2- 14C-DG autoradiography. Regions of interest were manually placed over cortical regions on corresponding coronal 18F-FDG PET and 2- 14C-DG autoradiographic images. rCMRglc values were calculated for both tracers by the autoradiographic 2-14C-DG method with modifications for the different rate and lumped constants for the 2 tracers. Results: Average rCMRglc values in cerebral cortex with 18F-FDG PET under normoglycemic conditions (isoflurane and awake) were generally lower (by 8.3%) but strongly correlated with those of 2- 14C-DG (r2 = 0.95). On the other hand, under hyperglycemic conditions (ketamine/xylazine) average cortical rCMRglc values with 18F-FDG PET were higher (by 17.3%) than those with 2- 14C-DG. Values for rCMRglc and uptake (percentage injected dose per gram [%ID/g]) with 18F-FDG PET were significantly lower under both isoflurane and ketamine/xylazine anesthesia than in the awake mice. However, the reductions of rCMRglc were markedly greater under isoflurane (by 57%) than under ketamine and xylazine (by 19%), whereas more marked reductions of %ID/g were observed with ketamine/xylazine (by 54%) than with isoflurane (by 37%). These reverse differences between isoflurane and ketamine/xylazine may be due to competitive effect of 18F-FDG and glucose uptake to the brain under hyperglycemia. Conclusion: We were able to obtain accurate absolute quantification of rCMRglc with mouse 18F-FDG PET imaging as confirmed by concurrent use of the autoradiographic 2-14C-DG method. Underestimation of rCMR glc by 18F-FDG in normoglycemic conditions may be due to partial-volume effects. Computation of rCMRglc from 18F-FDG data in hyperglycemic animals may require, however, alternative rate and lumped constants for 18F-FDG.

Original languageEnglish
Pages (from-to)1398-1405
Number of pages8
JournalJournal of Nuclear Medicine
Volume45
Issue number8
Publication statusPublished - 01-08-2004

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Fluorodeoxyglucose F18
Autoradiography
Glucose
Xylazine
Isoflurane
Ketamine
Brain
Anesthesia
Hyperglycemia
Cerebral Cortex

All Science Journal Classification (ASJC) codes

  • Radiological and Ultrasound Technology

Cite this

Toyama, Hiroshi ; Ichise, Masanori ; Liow, Jeih San ; Modell, Kendra J. ; Vines, Douglass C. ; Esaki, Takanori ; Cook, Michelle ; Seidel, Jurgen ; Sokoloff, Louis ; Green, Michael V. ; Innis, Robert B. / Absolute quantification of regional cerebral glucose utilization in mice by 18F-FDG small animal PET scanning and 2-14C-DG autoradiography. In: Journal of Nuclear Medicine. 2004 ; Vol. 45, No. 8. pp. 1398-1405.
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title = "Absolute quantification of regional cerebral glucose utilization in mice by 18F-FDG small animal PET scanning and 2-14C-DG autoradiography",
abstract = "The purpose of this study was to evaluate the feasibility of absolute quantification of regional cerebral glucose utilization (rCMRglc) in mice by use of 18F-FDG and a small animal PET scanner. rCMR glc determined with 18F-FDG PET was compared with values determined simultaneously by the autoradiographic 2-14C-DG method. In addition, we compared the rCMRglc values under isoflurane, ketamine and xylazine anesthesia, and awake states. Methods: Immediately after injection of 18F-FDG and 2-14C-DG into mice, timed arterial samples were drawn over 45 min to determine the time courses of 18F-FDG and 2-14C-DG. Animals were euthanized at 45 min and their brain was imaged with the PET scanner. The brains were then processed for 2- 14C-DG autoradiography. Regions of interest were manually placed over cortical regions on corresponding coronal 18F-FDG PET and 2- 14C-DG autoradiographic images. rCMRglc values were calculated for both tracers by the autoradiographic 2-14C-DG method with modifications for the different rate and lumped constants for the 2 tracers. Results: Average rCMRglc values in cerebral cortex with 18F-FDG PET under normoglycemic conditions (isoflurane and awake) were generally lower (by 8.3{\%}) but strongly correlated with those of 2- 14C-DG (r2 = 0.95). On the other hand, under hyperglycemic conditions (ketamine/xylazine) average cortical rCMRglc values with 18F-FDG PET were higher (by 17.3{\%}) than those with 2- 14C-DG. Values for rCMRglc and uptake (percentage injected dose per gram [{\%}ID/g]) with 18F-FDG PET were significantly lower under both isoflurane and ketamine/xylazine anesthesia than in the awake mice. However, the reductions of rCMRglc were markedly greater under isoflurane (by 57{\%}) than under ketamine and xylazine (by 19{\%}), whereas more marked reductions of {\%}ID/g were observed with ketamine/xylazine (by 54{\%}) than with isoflurane (by 37{\%}). These reverse differences between isoflurane and ketamine/xylazine may be due to competitive effect of 18F-FDG and glucose uptake to the brain under hyperglycemia. Conclusion: We were able to obtain accurate absolute quantification of rCMRglc with mouse 18F-FDG PET imaging as confirmed by concurrent use of the autoradiographic 2-14C-DG method. Underestimation of rCMR glc by 18F-FDG in normoglycemic conditions may be due to partial-volume effects. Computation of rCMRglc from 18F-FDG data in hyperglycemic animals may require, however, alternative rate and lumped constants for 18F-FDG.",
author = "Hiroshi Toyama and Masanori Ichise and Liow, {Jeih San} and Modell, {Kendra J.} and Vines, {Douglass C.} and Takanori Esaki and Michelle Cook and Jurgen Seidel and Louis Sokoloff and Green, {Michael V.} and Innis, {Robert B.}",
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Toyama, H, Ichise, M, Liow, JS, Modell, KJ, Vines, DC, Esaki, T, Cook, M, Seidel, J, Sokoloff, L, Green, MV & Innis, RB 2004, 'Absolute quantification of regional cerebral glucose utilization in mice by 18F-FDG small animal PET scanning and 2-14C-DG autoradiography', Journal of Nuclear Medicine, vol. 45, no. 8, pp. 1398-1405.

Absolute quantification of regional cerebral glucose utilization in mice by 18F-FDG small animal PET scanning and 2-14C-DG autoradiography. / Toyama, Hiroshi; Ichise, Masanori; Liow, Jeih San; Modell, Kendra J.; Vines, Douglass C.; Esaki, Takanori; Cook, Michelle; Seidel, Jurgen; Sokoloff, Louis; Green, Michael V.; Innis, Robert B.

In: Journal of Nuclear Medicine, Vol. 45, No. 8, 01.08.2004, p. 1398-1405.

Research output: Contribution to journal › Article

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T1 - Absolute quantification of regional cerebral glucose utilization in mice by 18F-FDG small animal PET scanning and 2-14C-DG autoradiography

AU - Toyama, Hiroshi

AU - Ichise, Masanori

AU - Liow, Jeih San

AU - Modell, Kendra J.

AU - Vines, Douglass C.

AU - Esaki, Takanori

AU - Cook, Michelle

AU - Seidel, Jurgen

AU - Sokoloff, Louis

AU - Green, Michael V.

AU - Innis, Robert B.

PY - 2004/8/1

Y1 - 2004/8/1

N2 - The purpose of this study was to evaluate the feasibility of absolute quantification of regional cerebral glucose utilization (rCMRglc) in mice by use of 18F-FDG and a small animal PET scanner. rCMR glc determined with 18F-FDG PET was compared with values determined simultaneously by the autoradiographic 2-14C-DG method. In addition, we compared the rCMRglc values under isoflurane, ketamine and xylazine anesthesia, and awake states. Methods: Immediately after injection of 18F-FDG and 2-14C-DG into mice, timed arterial samples were drawn over 45 min to determine the time courses of 18F-FDG and 2-14C-DG. Animals were euthanized at 45 min and their brain was imaged with the PET scanner. The brains were then processed for 2- 14C-DG autoradiography. Regions of interest were manually placed over cortical regions on corresponding coronal 18F-FDG PET and 2- 14C-DG autoradiographic images. rCMRglc values were calculated for both tracers by the autoradiographic 2-14C-DG method with modifications for the different rate and lumped constants for the 2 tracers. Results: Average rCMRglc values in cerebral cortex with 18F-FDG PET under normoglycemic conditions (isoflurane and awake) were generally lower (by 8.3%) but strongly correlated with those of 2- 14C-DG (r2 = 0.95). On the other hand, under hyperglycemic conditions (ketamine/xylazine) average cortical rCMRglc values with 18F-FDG PET were higher (by 17.3%) than those with 2- 14C-DG. Values for rCMRglc and uptake (percentage injected dose per gram [%ID/g]) with 18F-FDG PET were significantly lower under both isoflurane and ketamine/xylazine anesthesia than in the awake mice. However, the reductions of rCMRglc were markedly greater under isoflurane (by 57%) than under ketamine and xylazine (by 19%), whereas more marked reductions of %ID/g were observed with ketamine/xylazine (by 54%) than with isoflurane (by 37%). These reverse differences between isoflurane and ketamine/xylazine may be due to competitive effect of 18F-FDG and glucose uptake to the brain under hyperglycemia. Conclusion: We were able to obtain accurate absolute quantification of rCMRglc with mouse 18F-FDG PET imaging as confirmed by concurrent use of the autoradiographic 2-14C-DG method. Underestimation of rCMR glc by 18F-FDG in normoglycemic conditions may be due to partial-volume effects. Computation of rCMRglc from 18F-FDG data in hyperglycemic animals may require, however, alternative rate and lumped constants for 18F-FDG.

AB - The purpose of this study was to evaluate the feasibility of absolute quantification of regional cerebral glucose utilization (rCMRglc) in mice by use of 18F-FDG and a small animal PET scanner. rCMR glc determined with 18F-FDG PET was compared with values determined simultaneously by the autoradiographic 2-14C-DG method. In addition, we compared the rCMRglc values under isoflurane, ketamine and xylazine anesthesia, and awake states. Methods: Immediately after injection of 18F-FDG and 2-14C-DG into mice, timed arterial samples were drawn over 45 min to determine the time courses of 18F-FDG and 2-14C-DG. Animals were euthanized at 45 min and their brain was imaged with the PET scanner. The brains were then processed for 2- 14C-DG autoradiography. Regions of interest were manually placed over cortical regions on corresponding coronal 18F-FDG PET and 2- 14C-DG autoradiographic images. rCMRglc values were calculated for both tracers by the autoradiographic 2-14C-DG method with modifications for the different rate and lumped constants for the 2 tracers. Results: Average rCMRglc values in cerebral cortex with 18F-FDG PET under normoglycemic conditions (isoflurane and awake) were generally lower (by 8.3%) but strongly correlated with those of 2- 14C-DG (r2 = 0.95). On the other hand, under hyperglycemic conditions (ketamine/xylazine) average cortical rCMRglc values with 18F-FDG PET were higher (by 17.3%) than those with 2- 14C-DG. Values for rCMRglc and uptake (percentage injected dose per gram [%ID/g]) with 18F-FDG PET were significantly lower under both isoflurane and ketamine/xylazine anesthesia than in the awake mice. However, the reductions of rCMRglc were markedly greater under isoflurane (by 57%) than under ketamine and xylazine (by 19%), whereas more marked reductions of %ID/g were observed with ketamine/xylazine (by 54%) than with isoflurane (by 37%). These reverse differences between isoflurane and ketamine/xylazine may be due to competitive effect of 18F-FDG and glucose uptake to the brain under hyperglycemia. Conclusion: We were able to obtain accurate absolute quantification of rCMRglc with mouse 18F-FDG PET imaging as confirmed by concurrent use of the autoradiographic 2-14C-DG method. Underestimation of rCMR glc by 18F-FDG in normoglycemic conditions may be due to partial-volume effects. Computation of rCMRglc from 18F-FDG data in hyperglycemic animals may require, however, alternative rate and lumped constants for 18F-FDG.

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Toyama H, Ichise M, Liow JS, Modell KJ, Vines DC, Esaki T et al. Absolute quantification of regional cerebral glucose utilization in mice by 18F-FDG small animal PET scanning and 2-14C-DG autoradiography. Journal of Nuclear Medicine. 2004 Aug 1;45(8):1398-1405.

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