In Vivo Imaging of Local Inflammation: Monitoring LPS-Induced CD80/CD86 Upregulation by PET
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RESEARCH ARTICLE
In Vivo Imaging of Local Inflammation: Monitoring LPS-Induced CD80/CD86 Upregulation by PET Marco F. Taddio,1 Claudia A. Castro Jaramillo,1 Peter Runge,2 Alain Blanc,3 Claudia Keller,1 Zeynep Talip,3 Martin Béhé,3 Nicholas P. van der Meulen,3,4 Cornelia Halin,2 Roger Schibli,1,3 Stefanie D. Krämer 1 1
Center for Radiopharmaceutical Sciences ETH, PSI and USZ, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland 2 Pharmaceutical Immunology, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland 3 Center for Radiopharmaceutical Sciences ETH, PSI and USZ, Paul Scherrer Institute (PSI), Villigen, Switzerland 4 Laboratory of Radiochemistry, Paul Scherrer Institute (PSI), Villigen, Switzerland
Abstract Purpose: The co-stimulatory molecules CD80 and CD86 are upregulated on activated antigenpresenting cells (APC). We investigated whether local APC activation, induced by subcutaneous (s.c.) inoculation of lipopolysaccharides (LPS), can be imaged by positron emission tomography (PET) with CD80/CD86-targeting 64Cu-labelled abatacept. Procedures: Mice were inoculated s.c. with extracellular-matrix gel containing either LPS or vehicle (PBS). Immune cell populations were analysed by flow cytometry and marker expression by RT-qPCR. 64Cu-NODAGA-abatacept distribution was analysed using PET/CT and ex vivo biodistribution. Results: The number of CD80+ and CD86+ immune cells at the LPS inoculation site significantly increased a few days after inoculation. CD68 and CD86 expression were higher at the LPS than the PBS inoculation site, and CD80 was only increased at the LPS inoculation site. CTLA-4 was highest 10 days after LPS inoculation, when CD80/CD86 decreased again. A few days after inoculation, 64Cu-NODAGA-abatacept distribution to the inoculation site was significantly higher for LPS than PBS (4.2-fold). Co-administration of unlabelled abatacept or human immunoglobulin reduced tracer uptake. The latter reduced the number of CD86+ immune cells at the LPS inoculation site. Conclusions: CD80 and CD86 are upregulated in an LPS-induced local inflammation, indicating invasion of activated APCs. 64Cu-NODAGA-abatacept PET allowed following APC activation over time. Key words: Co-stimulatory molecules, CD80, CD86, PET, Abatacept, Lipopolysaccharides, Molecular imaging
Electronic supplementary material The online version of this article (https:// doi.org/10.1007/s11307-020-01543-3) contains supplementary material, which is available to authorized users. Correspondence to: Marco Taddio; e-mail: [email protected], Stefanie Krämer; e-mail: [email protected]
Taddio M. et al.: PET Imaging of CD80/CD86 in LPS-Induced Inflammation
Abbreviations: APC, antigen-presenting cell; CT, computed tomography; DC, dentridic cell; i.v, intravenous; LN, lymph node; LPS, lipopolysaccharides; NODAGA, 1,4,7-triazacyclononane,1glutaric acid-4,7-acetic acid; PB
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