Year: 2026
Type: article
Abstract: Innate immunity mediated by myeloid cells defends against infection and injury, but when chronically activated, it drives tissue damage and neurodegeneration. Molecular imaging with positron emission tomography (PET) enables noninvasive, real-time monitoring of such processes in vivo. However, most current neuroinflammation PET tracers lack specificity for activated myeloid cells. G protein–coupled receptor 84 (GPR84) is a promising biomarker that is selectively upregulated on activated microglia and macrophages. Here, we report the development and validation of two fluorine-18-labeled GPR84 tracers, [ 18 F]MGX-110S and [ 18 F]MGX-111S. Both exhibit specific binding to human GPR84-expressing cells, with [ 18 F]MGX-110S demonstrating superior affinity, selectivity, and signal-to-background ratio. [ 18 F]MGX-110S enables sensitive detection of systemic- and neuro-inflammation in LPS-treated mice and outperforms PET images obtained using a radiotracer specific for translocator protein 18 kDa in 5xFAD mice—revealing pathology-correlated activation across cortical, hippocampal, and thalamic regions. Taken together, our data indicate that [ 18 F]MGX-110S is a highly sensitive and specific tool for visualizing maladaptive myeloid cell activation; its clinical translation could enable more precise detection and staging of inflammation in addition to improved therapeutic monitoring in neurodegenerative disorders and more broadly in inflammatory diseases.
Authors: Mausam Kalita, Renesmee C. Kuo, Valentina Straniero, Samantha T. Reyes, Mallesh Pandrala, Alessia Lanzini, Sara Marsango, Desiree D’Moore, Piper Mahn, Andrew Setiadi, Mira Sundar, Spencer Mak, Sydney Nagy, Israt S. Alam, Poorva Jain, Grace Inay, Rim Malek, Allen F. Brooks, Corinne Beinat, Ermanno Valoti, Peter J. H. Scott, Graeme Milligan, Michelle L. James
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: National Science Foundation, Università degli Studi di Milano, Papua New Guinea University of Technology, National Institutes of Health, Directorate for Biological Sciences, Wu Tsai Neurosciences Institute, Stanford University, Biotechnology and Biological Sciences Research Council, National Institute on Aging, National Science Foundation Graduate Research Fellowship Program
OpenAlex ID: W7161949070