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Paper of the Month - September 2024
selected by the BMAS Scientific Board

[18F]F-AraG imaging reveals association between neuroinflammation and brown- and bone marrow adipose tissue

Jelena Levi1Caroline Guglielmetti2, 3, 4, Timothy J Henrich5John C Yoon6Prafulla C Gokhale7David A Reardon7Juliet Packiasamy8Lyna Huynh8 Hilda Cabrera8Marisa Ruzevich8Joseph Blecha3Michael J Peluso9Tony L Huynh3Sung-Min An6Mark Dornan10Anthony P Belanger10Quang-Dé Nguyen11Youngho Seo3Hong Song12Myriam M Chaumeil2, 3Henry F VanBrocklin3Hee-Don Chae8

1 CellSight Technologies Incorporated, San Francisco, CA, USA. jlevi@cellsighttech.com. 2 Department of Physical Therapy and Rehabilitation Science, University of California San Francisco, San Francisco, CA, USA. 3 Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA. 4 Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO, USA. 5 Division of Experimental Medicine, University of California San Francisco, San Francisco, CA, USA. 6 Division of Endocrinology, Department of Internal Medicine, University of California Davis School of Medicine, Davis, CA, USA. 7 Dana-Farber Cancer Institute, Boston, MA, USA. 8 CellSight Technologies Incorporated, San Francisco, CA, USA. 9 Division of HIV, ID and Global Medicine, University of California San Francisco, San Francisco, CA, USA. 10 Molecular Cancer Imaging Facility, Dana-Farber Cancer Institute, Boston, MA, USA. 11 Lurie Family Imaging Center, Dana-Farber Cancer Institute, Boston, MA, USA. 12 Department of Radiology, Stanford University, Palo Alto, CA, USA.

PMID: 38951146 | PMCID: PMC11217368  | https://rdcu.be/dVDAl DOI:10.1038/s42003-024-06494-x

ABSTRACT

Brown and brown-like adipose tissues have attracted significant attention for their role in metabolism and therapeutic potential in diabetes and obesity. Despite compelling evidence of an interplay between adipocytes and lymphocytes, the involvement of these tissues in immune responses remains largely unexplored. This study explicates a newfound connection between neuroinflammation and brown- and bone marrow adipose tissue. Leveraging the use of [18F]F-AraG, a mitochondrial metabolic tracer capable of tracking activated lymphocytes and adipocytes simultaneously, we demonstrate, in models of glioblastoma and multiple sclerosis, the correlation between intracerebral immune infiltration and changes in brown- and bone marrow adipose tissue. Significantly, we show initial evidence that a neuroinflammation-adipose tissue link may also exist in humans. This study proposes the concept of an intricate immuno-neuro-adipose circuit, and highlights brown- and bone marrow adipose tissue as an intermediary in the communication between the immune and nervous systems. Understanding the interconnectedness within this circuitry may lead to advancements in the treatment and management of various conditions, including cancer, neurodegenerative diseases and metabolic disorders.

Fig. 1 | [18F]F-AraG accumulates in adrenergically stimulated brown fat and bone
marrow.
Fig. 6: Simultaneous imaging of activated lymphocytes and adipocytes with [18F]F-AraG reveals concurrent neuroinflammation and BAT activation in a post-acute COVID subject.