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.
Pharmaceutical Immunology, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
Mol Imaging Biol. 2021 Apr;23(2):196-207. doi: 10.1007/s11307-020-01543-3. Epub 2020 Sep 28.
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 Cu-labelled abatacept.
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. Cu-NODAGA-abatacept distribution was analysed using PET/CT and ex vivo biodistribution.
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, 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.
CD80 and CD86 are upregulated in an LPS-induced local inflammation, indicating invasion of activated APCs. Cu-NODAGA-abatacept PET allowed following APC activation over time.
共刺激分子 CD80 和 CD86 在激活的抗原呈递细胞 (APC) 上上调。我们研究了通过皮下 (s.c.) 接种脂多糖 (LPS) 诱导局部 APC 激活是否可以通过正电子发射断层扫描 (PET) 用 CD80/CD86 靶向 Cu 标记的阿巴西普进行成像。
将小鼠用含有 LPS 或载体 (PBS) 的细胞外基质凝胶皮下接种。通过流式细胞术分析免疫细胞群，并通过 RT-qPCR 分析标志物表达。使用 PET/CT 和离体生物分布分析 Cu-NODAGA-abatacept 的分布。
接种 LPS 后几天，LPS 接种部位的 CD80 和 CD86 免疫细胞数量显著增加。与 PBS 接种部位相比，LPS 接种部位的 CD68 和 CD86 表达更高，而 CD80 仅在 LPS 接种部位增加。CTLA-4 在 LPS 接种后 10 天最高，此时 CD80/CD86 再次下降。接种后几天，LPS 接种部位的 Cu-NODAGA-abatacept 分布明显高于 PBS（4.2 倍）。未标记的阿巴西普或人免疫球蛋白的共同给药减少了示踪剂摄取。后者减少了 LPS 接种部位的 CD86 免疫细胞数量。
LPS 诱导的局部炎症中 CD80 和 CD86 上调，表明活化的 APC 入侵。Cu-NODAGA-abatacept PET 允许随时间监测 APC 激活。
