Abstract
Conventional MR imaging (MRI) techniques form the cornerstone of multiple sclerosis (MS) diagnostics and clinical follow-up today. MRI is sensitive in demonstrating focal inflammatory lesions and diffuse atrophy. However, especially in progressive MS, there is increasingly widespread diffuse pathology also outside the plaques, often related to microglial activation and neurodegeneration. This cannot be detected using conventional MRI. Positron emission tomography (PET) imaging using 18-kDa translocator protein (TSPO) binding radioligands has recently shown promise as a tool to detect this diffuse pathology in vivo, and for the first time allows one to follow its development longitudinally. It is becoming evident that the more advanced the MS disease is, the more pronounced is microglial activation. PET imaging allows the detection of MS-related pathology at molecular level in vivo. It has potential to enable measurement of effects of new disease-modifying drugs aimed at reducing neurodegeneration and neuroinflammation. PET imaging could thus be included in the design of future clinical trials of progressive MS. There are still technical issues related to the quality of TSPO radioligands and post-processing methodology, and comparison of studies from different PET centres is challenging. In this review, we summarise the main evidence supporting the use of TSPO-PET as a tool to explore the diffuse inflammation in MS.
Highlights
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), where neuroinflammation and neurodegeneration are the two main components in the pathogenesis
In accordance with the results with [11C]PBR28, a study with [18F]PBR111 [67], where the subjects were matched according to their translocator protein (TSPO) binding genotype, showed that the TSPO binding was increased in the T2 lesional and perilesional WM of relapsing– remitting MS (RRMS) patients (n = 11) when compared to healthy controls (n = 11), and the ratio of VT in the T2-lesional WM versus normal appearing white matter (NAWM) appeared to correlate with the disease severity
In our in vivo Positron emission tomography (PET) studies of secondary progressive MS (SPMS) patients, we demonstrated that TSPO imaging can be used to differentiate the chronic active and chronic inactive plaques in vivo, a manifestation of microglial cell activation not detectable by MR imaging (Figs. 1, 2)
Summary
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), where neuroinflammation and neurodegeneration are the two main components in the pathogenesis. In some lesions, a focal increase in [11C]PBR28 binding preceded the appearance of gadolinium enhancement, pointing to a role for early glial activation in MS lesion development [62] Another pilot study with 4 RRMS patients detected similar patterns of TSPO binding with the second-generation TSPO ligand [11C]vinpocetine when compared to [11C](R)-PK11195, but with higher binding potentials and a better signal-to-noise ratio [64]. In accordance with the results with [11C]PBR28, a study with [18F]PBR111 [67], where the subjects were matched according to their TSPO binding genotype, showed that the TSPO binding was increased in the T2 lesional and perilesional WM of RRMS patients (n = 11) when compared to healthy controls (n = 11), and the ratio of VT in the T2-lesional WM versus NAWM appeared to correlate with the disease severity (measured with the multiple sclerosis severity scale, MSSS) These results suggest that TSPO-PET could be used for monitoring pharmacological effects targeting neuroinflammation.
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