Abstract
Multiple sclerosis (MS) is a chronic neurodegenerative disease driven by infiltration of activated innate immune cells into the central nervous system (CNS). Current imaging approaches for diagnosing and monitoring disease progression rely on structural lesions and cannot directly assess innate immune activity. Here, we describe a dendrimer positron emission tomography (PET) tracer, 18F-flurimedrimer (18F-FMD), for non-invasive, longitudinal tracking of activated myeloid cells. In an experimental autoimmune encephalomyelitis (EAE) murine model, 18F-FMD specifically detects myeloid activation at presymptomatic and symptomatic stages, with PET signal correlating with disease severity. Moreover, 18F-FMD sensitively captures therapeutic response to fingolimod (FTY720) and a CSF1R dendranib (H74DS3M8), both of which suppress immune cell activation and attenuate disease severity. These findings highlight the potential of 18F-FMD PET for specific, real-time monitoring of innate immune responses, and the applicability of the dendrimer in clinical settings for monitoring therapeutic efficacy, advancing the development of personalized, myeloid-targeted strategies for MS.
Data availability
All data are included in the Supplementary Information or available from the authors, as are unique reagents used in this Article. The raw numbers for charts and graphs are available in the Source Data file whenever possible. The raw PET imaging and flow cytometry data generated in this study have been deposited in the Figshare database under https://doi.org/10.6084/m9.figshare.30644609. Source data are provided with this paper.
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Acknowledgements
We would like to thank Dr. Emily Becker for her assistance in preparing the manuscript. This work was supported by Ashvattha Therapeutics (to M.L.J.), NIH/NINDS (grant number: 1R21NS135513-01A1, to M.L.J.) and NSF GRFP (grant number: DGE-2146755, to R.C.K.).
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R.C.K. and M.L.C. designed and implemented the study, led data acquisition and analysis, and wrote the manuscript and prepared all figures and tables. S.T.R., S.C.N., M.K., I.S.A., C.J.A., I.N.F., E.C.A., C.B., and M.C. helped with data acquisition. N.M. and I.M.J. synthesized the radiotracer. Y.Z. and L.N. at the Stanford Shared FACS Facility designed the flow cytometry panel and provided guidance on data analysis. N.G.A., S.S.M., and J.L.C. helped conceptualize and design the study and analysis. M.L.J. helped design the study and assisted with developing figures and interpreting data. All authors reviewed the manuscript.
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N.G.A., M.C., S.S.M., and J.L.C. are employed by Ashvattha Therapeutics during the completion of this work. All other authors have declared no conflicts of interest.
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Kuo, R.C., Carlson, M.L., Reyes, S.T. et al. A radiolabeled dendrimer non-invasively identifies and tracks innate immune cell activation in a mouse model of experimental autoimmune encephalomyelitis. Nat Commun (2026). https://doi.org/10.1038/s41467-025-67907-x
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DOI: https://doi.org/10.1038/s41467-025-67907-x
