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18F-FDG PET detects inflammatory infiltrates in spinal cord experimental autoimmune encephalomyelitis lesions
Dorothea Buck1, Annette Förschler, Constantin Lapa
1Department of Neurology, Technische Universität München, Munich, Germany.
Unlabelled:
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-(18)F-fluoro-2-deoxy-d-glucose ((18)F-FDG), 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT), and O-(2-(18)F-fluoro-ethyl)-l-tyrosine ((18)F-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 (18)F-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 (18)F-FDG signal intensity in PET (F(DF=3) = 5.9, P = 0.001) and autoradiography (F(DF=3) = 4.2, P = 0.008). With (18)F-FET and (18)F-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 (18)F-FDG PET/CT. Localized (18)F-FDG uptake correlates better with a histologically proven abundance of inflammatory cells as a critical marker of disease activity than MRI. Neither (18)F-FET nor (18)F-FLT seems to be a suitable marker for the in vivo detection of inflammatory lesions.
Insights
This study shows that MRI and 18F-FDG PET/CT can visualize multiple sclerosis lesions in rats. 18F-FDG uptake correlates with inflammatory cell density, offering a better disease activity marker than MRI alone.
Area of Science:
- Neuroscience
- Medical Imaging
- Immunology
Background:
- Multiple sclerosis (MS) is a complex neurological disease characterized by varied lesion pathology, disease progression, and treatment responses.
- Advanced imaging techniques are crucial for precise in vivo characterization of MS lesions.
- Experimental autoimmune encephalomyelitis (EAE) serves as a valuable animal model for studying MS.
Purpose of the Study:
- To develop and evaluate an integrated MRI and PET/CT imaging approach for MS.
- To assess the utility of approved and novel PET tracers in the EAE model.
- To correlate imaging findings with histological and molecular markers of disease activity.
Main Methods:
- MRI and PET/CT scans were performed on Dark agouti rats with EAE and healthy controls.
- PET tracers evaluated included 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).
- Post-scan analyses included autoradiography, histology, and RNA expression analysis.
Main Results:
- MRI successfully detected inflammatory lesions in EAE rats, correlating with histological findings.
- Increased 18F-FDG uptake was observed in spinal cord lesions of EAE rats.
- 18F-FDG PET signal intensity correlated significantly with the density of inflammatory cells (P = 0.001) and autoradiography findings (P = 0.008).
- 18F-FET and 18F-FLT showed minimal uptake on PET scans, with only slight accumulation noted in some lesions via autoradiography.
Conclusions:
- Combined MRI and 18F-FDG PET/CT effectively visualize spinal cord inflammatory lesions in the EAE model.
- 18F-FDG uptake provides a more accurate measure of inflammatory cell abundance and disease activity than MRI alone.
- 18F-FET and 18F-FLT are not suitable for in vivo detection of inflammatory lesions in this model.
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