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 journalArticle

83 Citations (Scopus)

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

Fingerprint

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.
@article{04ac0d69e9ed4868bb92c3d935e0fbdd,
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.}",
year = "2004",
month = "8",
day = "1",
language = "English",
volume = "45",
pages = "1398--1405",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "Society of Nuclear Medicine Inc.",
number = "8",

}

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 journalArticle

TY - JOUR

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.

UR - http://www.scopus.com/inward/record.url?scp=4544383535&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4544383535&partnerID=8YFLogxK

M3 - Article

C2 - 15299067

AN - SCOPUS:4544383535

VL - 45

SP - 1398

EP - 1405

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

IS - 8

ER -