Imaging of microglial activation in MS using PET: Research use and potential future clinical application

Abstract

MS is a complex disease, where several processes can be selected as a target for PET imaging. Unlike MRI, PET provides specific and quantitative information, and unlike neuropathology, it can be non-invasively applied to living patients, which enables longitudinal follow-up of the MS pathology. In the study of MS, PET can be useful for in vivo evaluation of specific pathological characteristics at various stages of the disease. Increased understanding of the progressive MS pathology will enhance the treatment options of this undertreated condition. The ultimate goal of developing and expanding PET in the study of MS is to have clinical non-invasive in vivo imaging biomarkers of neuroinflammation that will help to establish prognosis, and accurately measure response to therapeutics. This topical review provides an overview of the promises and challenges of the use of PET in MS.

Molecular Imaging of Neuroinflammation in Neurodegenerative Dementias: The Role of In Vivo PET Imaging

“…11 C-PK11195 is by far the most validated and adopted in human studies [41]. It has been used to explore patterns of neuroinflammation both in healthy subjects and in neurological diseases, including neurodegenerative conditions [10,42,43,44,45,46]. 11 C-PK11195 presents, however, some limits, such as highly lipophilic nature, low bioavailability, high non-specific binding and limited capacity to detect small changes in TSPO expression, which led to a recent effort towards the development of second-generation TSPO ligands [41].…”

A new frontier for amyloid PET imaging: multiple sclerosis

“…Molecular imaging techniques based on PET have also been tested in MS patients [13]. Experience in this setting has been based on tracers targeting neuroinflammation as well as microglia/monocyte activation and invasion in the CNS [14].…”

TSPO-PET Imaging to Assess Cerebral Microglial Activation in Multiple Sclerosis

“…While several molecular targets for such imaging have been proposed, 18 the bulk of the literature focuses on TSPO ligands to quantify microglial activation. 19 Translocator Protein as a Molecular Target for PET Imaging…”

“…(1) Study design: While several cross-sectional PET measurements of microglial activation have been reported using various TSPO-targeted ligands, longitudinal assessment of microglial activation has not been comprehensively eval-uated. 18,19 Similarly, studies need to be designed to address clinically meaningful questions, such as assessing the role of PET imaging in therapy selection, prognostication, and assessment of treatment efficacy. (2) Improved TSPO-PET ligands: Most studies performed to date using [C-11] ligands have practical and technical limitations.…”