In Vivo Imaging of Local Inflammation: Monitoring LPS-Induced CD80/CD86 Upregulation by PET

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 (64)Cu-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. (64)Cu-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, (64)Cu-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. (64)Cu-NODAGA-abatacept PET allowed following APC activation over time. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11307-020-01543-3) contains supplementary material, which is available to authorized users.