Clinical translation of a new PET radiotracer for mapping innate immune activation in multiple sclerosis and other neurodegenerative diseases

Multiple sclerosis (MS) is a chronic, demyelinating, neuroinflammatory disease typically affecting young adults, causing substantial morbidity and diminished quality of life. Although multiple disease-modifying immunomodulatory therapies are available for MS, disease manifestations and treatment response are highly variable and difficult to predict in patients. Current standard of care imaging techniques used to diagnose and monitor MS cannot provide early and specific molecular information regarding an individual’s immune signature in the central nervous system (CNS), thus limiting our ability to select the most appropriate therapy and obtain early predictors of response for any given patient. This increases economic burden on MS patients and their families as they often must try several therapies before finding what works best to manage their disease. Hence there is a need for non-invasive molecular imaging strategies that provide real-time endpoints about specific immune cells and their functional phenotypes in MS patients to help speed the selection of the right therapy for a given individual. Myeloid cells are fundamental to the progression and remission of MS; activated macrophages and microglia are the predominant immune cells associated with acute and chronic-active CNS lesions. Unfortunately, existing imaging strategies for detecting activated microglia and macrophages lack specificity and cannot distinguish between beneficial (anti-inflammatory) and toxic (pro-inflammatory) immune responses. To address this limitation, we recently identified GPR84 as a selective imaging biomarker of proinflammatory macrophages and microglia. Our proposal to assess two promising PET radiotracers head-to-head in human cells/tissues and a mouse model of MS will result in the selection of a lead radiotracer to translate for clinical imaging. Our technology, known as GPR84-PET imaging, could have far-reaching and significant impact as a molecular imaging technique for mapping toxic innate immune activation with high specificity in a range of neurological diseases to improve disease staging and therapy selection, thus improving outcomes for patients and decreasing financial burden.