Positron emission tomography with computed tomography imaging of neuroinflammation in experimental autoimmune encephalomyelitis

doi:10.1073/pnas.0610544104

Positron emission tomography with computed tomography imaging of neuroinflammation in experimental autoimmune encephalomyelitis

Departments of *Molecular and Medical Pharmacology and
^†Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine,
^‡Institute for Molecular Medicine,
^§Institute for Stem Cell Biology and Medicine, and
^¶Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095

Contributed by Owen N. Witte, November 28, 2006 (received for review November 6, 2006)

Abstract

2-[¹⁸F]Fluoro-2-deoxy-d-glucose positron emission tomography ([¹⁸F]FDG PET) detection of the up-regulated glycolysis associated with malignant transformation is a noninvasive imaging technique used extensively in cancer diagnosis. Although striking similarities exist in glucose transport and metabolism between tumor cells and activated immune cells, the potential use of [¹⁸F]FDG PET for the diagnosis and evaluation of autoimmune disorders has not been systematically investigated. Here we ask whether [¹⁸F]FDG PET in conjunction with computed tomography (CT) could be used to monitor a complex autoimmune disorder such as murine experimental autoimmune encephalomyelitis (EAE) and whether this approach is sensitive enough to evaluate therapeutic interventions. We found that (i) coregistration of metabolic (i.e., microPET) and high-resolution anatomical (i.e., CT) images allows serial quantification of glycolysis with [¹⁸F]FDG in various spinal column segments; (ii) [¹⁸F]FDG PET/CT can detect the increased glycolysis associated with paralysis-causing inflammatory infiltrates in the spinal cord; and (iii) the [¹⁸F]FDG measure of glycolysis in the spinal cord is sensitive to systemic immunosuppressive therapy. These results highlight the potential use of serial [¹⁸F]FDG PET/CT imaging to monitor neuroinflammation in EAE and suggest that similar approaches could be applied to the diagnosis and evaluation of other autoimmune and inflammatory disorders in animal models and in humans.

Footnotes

^‖To whom correspondence should be addressed at:
Howard Hughes Medical Institute, University of California at Los Angeles, 675 Charles E. Young Drive South, 5-748 MRL Building, Los Angeles, CA 90095-1662.
E-mail: owenw{at}microbio.ucla.edu
Author contributions: C.G.R. and C.J.S. contributed equally to this work; C.G.R., C.J.S., M.E.P., and O.N.W. designed research; C.G.R., C.J.S., and S.M.S. performed research; C.G.R., C.J.S., and S.M.S. analyzed data; and C.G.R. wrote the paper.
The authors declare no conflict of interest.
Abbreviations:

PET,

positron emission tomography [18F]FDG, 2-[18F]fluoro-2-deoxy-d-glucose;

CT,

computed tomography;

EAE,

experimental autoimmune encephalomyelitis;

MOG,

myelin oligodendrocyte glycoprotein;

CFA,

complete Freund's adjuvant;

PTX,

pertussis toxin;

ROI,

region of interest;

14C-DG,

14C-labeled 2-deoxy-d-glucose;

DEX,

dexamethasone;

MS,

multiple sclerosis.
Freely available online through the PNAS open access option.