&lt;em&gt;In vivo&lt;/em&gt; imaging of local inflammation: monitoring LPS-induced CD80/CD86 upregulation by PET

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.

doi:10.1007/s11307-020-01543-3

In vivo imaging of local inflammation: monitoring LPS-induced CD80/CD86 upregulation by PET

Taddio MF, Castro Jaramillo CA, Runge P, Blanc A, Keller C, Talip Z, Béhé M, van der Meulen NP, Halin C, Schibli R & Krämer SD

Citation

Taddio, M. F., Castro Jaramillo, C. A., Runge, P., Blanc, A., Keller, C., Talip, Z., … Krämer, S. D. (2021). In vivo imaging of local inflammation: monitoring LPS-induced CD80/CD86 upregulation by PET. Molecular Imaging and Biology, 23, 196-207. https://doi.org/10.1007/s11307-020-01543-3

Persistent URL https://www.dora.lib4ri.ch/psi/islandora/object/psi:34498

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.