TY - JOUR
T1 - 18F-FDG PET detects inflammatory infiltrates in spinal cord experimental autoimmune encephalomyelitis lesions
AU - Buck, Dorothea
AU - Förschler, Annette
AU - Lapa, Constantin
AU - Schuster, Tibor
AU - Vollmar, Patrick
AU - Korn, Thomas
AU - Nessler, Stefan
AU - Stadelmann, Christine
AU - Drzezga, Alexander
AU - Buck, Andreas K.
AU - Wester, Hans Jürgen
AU - Zimmer, Claus
AU - Krause, Bernd Joachim
AU - Hemmer, Bernhard
PY - 2012/8/1
Y1 - 2012/8/1
N2 - Multiple sclerosis (MS) is a heterogeneous disease with respect to lesion pathology, course of disease, and treatment response. Imaging modalities are needed that allow better definition of MS lesions in vivo. The aim of this study was to establish an MRI- and PET/CT-based imaging modality and to evaluate approved and promising PET tracers in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. Methods: MRI and PET/CT scans were obtained in Dark agouti rats with EAE and healthy control rats. The PET tracers 2- 18F-fluoro-2-deoxy-D-glucose ( 18F-FDG), 3′-deoxy-3′- 18F-fluorothymidine ( 18F-FLT), and O-(2- 18F-fluoro-ethyl)-L-tyrosine ( 18F-FET) were used as surrogate markers of glucose utilization, proliferative activity, and amino acid transport and protein biosynthesis. Immediately after the PET/CT scan, animals were sacrificed for autoradiography, histologic work-up, or RNA expression analysis. Results: EAE lesions were predominantly located in the spinal cord. With MRI, we were able to detect inflammatory lesions in diseased rats, which correlated well with inflammatory infiltrates as determined by histology. Increased 18F-FDG uptake was observed in spinal cord lesions in all diseased rats. Further investigation by volume-of-interest analysis demonstrated a correlation between the density of histologically proven cellular infiltrates and the 18F-FDG signal intensity in PET (F DF=3 = 5.9, P = 0.001) and autoradiography (F DF=3 = 4.2, P = 0.008). With 18F-FET and 18F-FLT, no definite uptake could be observed on PET scans, whereas autoradiography showed slight radiotracer accumulation in some lesions. Conclusion: Spinal cord inflammatory lesions in the EAE model can be noninvasively visualized in vivo using MRI and 18F-FDG PET/CT. Localized 18F-FDG uptake correlates better with a histologically proven abundance of inflammatory cells as a critical marker of disease activity than MRI. Neither 18F-FET nor 18F-FLT seems to be a suitable marker for the in vivo detection of inflammatory lesions.
AB - Multiple sclerosis (MS) is a heterogeneous disease with respect to lesion pathology, course of disease, and treatment response. Imaging modalities are needed that allow better definition of MS lesions in vivo. The aim of this study was to establish an MRI- and PET/CT-based imaging modality and to evaluate approved and promising PET tracers in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. Methods: MRI and PET/CT scans were obtained in Dark agouti rats with EAE and healthy control rats. The PET tracers 2- 18F-fluoro-2-deoxy-D-glucose ( 18F-FDG), 3′-deoxy-3′- 18F-fluorothymidine ( 18F-FLT), and O-(2- 18F-fluoro-ethyl)-L-tyrosine ( 18F-FET) were used as surrogate markers of glucose utilization, proliferative activity, and amino acid transport and protein biosynthesis. Immediately after the PET/CT scan, animals were sacrificed for autoradiography, histologic work-up, or RNA expression analysis. Results: EAE lesions were predominantly located in the spinal cord. With MRI, we were able to detect inflammatory lesions in diseased rats, which correlated well with inflammatory infiltrates as determined by histology. Increased 18F-FDG uptake was observed in spinal cord lesions in all diseased rats. Further investigation by volume-of-interest analysis demonstrated a correlation between the density of histologically proven cellular infiltrates and the 18F-FDG signal intensity in PET (F DF=3 = 5.9, P = 0.001) and autoradiography (F DF=3 = 4.2, P = 0.008). With 18F-FET and 18F-FLT, no definite uptake could be observed on PET scans, whereas autoradiography showed slight radiotracer accumulation in some lesions. Conclusion: Spinal cord inflammatory lesions in the EAE model can be noninvasively visualized in vivo using MRI and 18F-FDG PET/CT. Localized 18F-FDG uptake correlates better with a histologically proven abundance of inflammatory cells as a critical marker of disease activity than MRI. Neither 18F-FET nor 18F-FLT seems to be a suitable marker for the in vivo detection of inflammatory lesions.
KW - EAE
KW - MRI
KW - Multiple sclerosis
KW - PET
UR - http://www.scopus.com/inward/record.url?scp=84864776548&partnerID=8YFLogxK
U2 - 10.2967/jnumed.111.102608
DO - 10.2967/jnumed.111.102608
M3 - Article
C2 - 22738927
AN - SCOPUS:84864776548
SN - 0161-5505
VL - 53
SP - 1269
EP - 1276
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 8
ER -