Author/Authors :
Tang, Tang University of California - Davis, USA , Valenzuela, Anthony Department of Neurology - School of Medicine - University of California Davis - Sacramento, USA , Petit, Fanny Universite Paris-Sud - Universite Paris-Saclay - Fontenay-aux-Roses, France , Chow, Sarah Department of Biomedical Engineering - University of California - Davis, USA , Leung, Kevin Department of Biomedical Engineering - University of California - Davis, USA , Gorin, Fredric Department of Neurology - School of Medicine - University of California Davis - Sacramento, USA , Louie, Angelique Y University of California - Davis, USA , Dhenain, Marc Universite Paris-Sud - Universite Paris-Saclay - Fontenay-aux-Roses, France
Abstract :
Microglia are intrinsic components of the brain immune system and are activated in many central nervous system disorders. The
ability to noninvasively image these cells would provide valuable information for both research and clinical applications. Today,
most imaging probes for activated microglia are mainly designed for positron emission tomography (PET) and target translocator
proteins that also reside on other cerebral cells. The PETimages obtained are not specific for microglia-driven inflammation. Here,
we describe a potential PET/MRI multimodal imaging probe that selectively targets the scavenger receptor class A (SR-A)
expressed on activated microglia. These sulfated dextran-coated iron oxide (SDIO) nanoparticles are avidly taken up by microglia
and appear to be nontoxic when administered intravenously in a mouse model. Intravenous administration of this SDIO
demonstrated visualization by T∗
2 -weighted MRI of microglia activated by intracerebral administration of tumor necrosis factor
alpha (TNF-α). The contrast was significantly enhanced by SDIO, whereas there was little to no contrast change in animals treated
with nontargeted nanoparticles or untreated controls. Thus, SR-A targeting represents a promising strategy to image activated
microglia in the brain.