Radiolabeled dendrimer non-invasively tracks innate immune activation in multiple sclerosis mice after immunomodulatory therapy

Multiple sclerosis (MS) is a chronic neurodegenerative disease driven by immune cell infiltration into the central nervous system (CNS). Despite the critical role of immune cells in MS initiation and progression, current standard of care imaging techniques rely on structural lesion assessments, often resulting in misdiagnoses and inaccurate disease staging. Here we describe a novel dendrimer positron emission tomography (PET) tracer, ¹⁸ F-flurimedrimer ( ¹⁸ F-FMD), for non-invasive detection and tracking of activated myeloid cells–key immune players in MS. Using an experimental autoimmune encephalomyelitis (EAE) murine model of MS, we demonstrate the ability of ¹⁸ F-FMD to specifically detect these cells at both presymptomatic and symptomatic stages, with signal intensity correlating with disease severity. We illustrate that ¹⁸ F-FMD can also accurately monitor the immunomodulatory effects of Food and Drug Administration (FDA)-approved disease-modifying MS drug fingolimod (FTY720) and a novel CSF1R dendranib (H74DS3M8), both of which reduced immune cell activation and halted disease progression. These findings highlight the potential of ¹⁸ F-FMD PET for early MS diagnosis and as a generalizable approach for real-time monitoring of therapeutic responses across various mechanisms. Since we have translated ¹⁸ F-FMD for clinical imaging, it has the potential to revolutionize patient stratification in clinical trials and optimize treatments, making precision medicine a reality for MS patients.