A recent study published in Annals of Neurology revealed that [18F]-DPA-714-PET effectively classified white matter multiple sclerosis (MS) lesions as per the activated innate immune cells density and localization. The study highlighted that [18F]-DPA-714-PET demonstrated an unexpectedly high proportion of MS lesions having a smoldering component responsible for predicting atrophy and clinical progression.
The researchers enrolled 36 people with MS (PwMS) having a disease duration of 9 years and comprising 12 relapsing-remitting, 13 secondary-progressive, 11 primary-progressive patients, and 19 healthy controls (HC). All patients underwent a dynamic [18F]-DPA-714-PET followed by MRI and neurological examination after 2 years. The white matter lesions were classified based on a threshold of significant inflammation as either homogeneously active (active center), rim-active (inactive center and active periphery), or nonactive.
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Study results showed that PwMS reported higher innate inflammation in normal appearing white matter (NAWM) and cortex compared to the HC (P= .003). Moreover, out of 1335 nongadolinium-enhancing lesions, 707 (53%) were classified as homogeneously-active, while 80 (6%) were rim-active, and 547 (41%) were nonactive lesions.
In addition, the number of homogenously-active lesions were the strongest in predicting longitudinal changes associated with cortical atrophy and Expanded Disability Status Scale changes over the 2 years. Furthermore, no association was found between cortical binding and NAWM to volumetric and clinical changes.
“We found here that homogeneously-active lesions played a predominant role on atrophy progression and disability worsening over 2 years”, the authors wrote. “Our results encourage reconsidering the prognostic value of MS lesion phenotypes on disease trajectories, in light of their heterogeneity regarding persisting neuroinflammation and repair,” the authors further added.
In MS, neurodegeneration begins early in the disease course and is largely independent of acute inflammation driven by the adaptive immune system. Identifying the mechanisms involved in neurodegeneration and predicting individual clinical trajectories in PwMS remain major challenges. Innate immune cell mediated neuroinflammation, mainly microglia, is believed to play a central role in the neurodegenerative process in MS. However, the persistence of neuroinflammation mechanisms is not well understood. Choroid plexuses, which are enlarged and inflamed in PwMS with inflammatory profiles, may contribute to this process.
Positron emission tomography (PET) with radiotracers targeting the 18-kDA translocator protein (TSPO) allows for the selective quantification of innate immune cell density in the central nervous system. Prior studies utilizing TSPO radiopharmaceuticals in MS have reported increased binding in lesions and normal appearing tissues of PwMS than HCs, correlating with disease severity.
Several studies have suggested that TSPO-PET can be used to identify chronic active lesions, which can be found at every stage of the disease. However, the long-term prognostic value of different lesional stages identified by PET remains poorly explored.
Reference
Hamzaoui M, Garcia J, Boffa G, et al. Positron emission tomography with [18F]-DPA-714 unveils a smoldering component in most multiple sclerosis lesions which drives disease progression. Ann Neurol. Published online Apr 11, 2023. doi:10.1002/ana.26657
