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- Title
In Vivo Imaging of Local Inflammation: Monitoring LPS-Induced CD80/CD86 Upregulation by PET.
- Authors
Taddio, Marco F.; Castro Jaramillo, Claudia A.; Runge, Peter; Blanc, Alain; Keller, Claudia; Talip, Zeynep; Béhé, Martin; van der Meulen, Nicholas P.; Halin, Cornelia; Schibli, Roger; Krämer, Stefanie D.
- Abstract
Purpose: The co-stimulatory molecules CD80 and CD86 are upregulated on activated antigen-presenting 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.
- Subjects
TRANSLOCATOR proteins; POSITRON emission tomography; INFLAMMATION; CELL populations
- Publication
Molecular Imaging & Biology, 2021, Vol 23, Issue 2, p196
- ISSN
1536-1632
- Publication type
Article
- DOI
10.1007/s11307-020-01543-3