期刊
MOLECULAR IMAGING
卷 18, 期 -, 页码 -出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/1536012119829986
关键词
immuno-PET imaging; PD-L1; anti-PD-L1 antibodies; avelumab; [Zr-89]Zr-DFO-PD-L1 mAb
资金
- National Cancer Institute, National Institutes of Health [HHSN261200800001E]
- NATIONAL CANCER INSTITUTE [ZIABC010668] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [ZICHL005090] Funding Source: NIH RePORTER
Objective: The goal is to evaluate avelumab, an anti-PD-L1 monoclonal immunoglobulin G antibody labeled with zirconium-89 in human PD-L1-expressing cancer cells and mouse xenografts for clinical translation. Methods: [Zr-89]Zr-DFO-PD-L1 monoclonal antibody (mAb) was synthesized using avelumab conjugated to desferrioxamine. In vitro binding studies and biodistribution studies were performed with PD-L1+MDA-MB231 cells and MDA-MB231 xenograft mouse models, respectively. Biodistributions were determined at 1, 2, 3, 5, and 7 days post coinjection of [Zr-89]Zr-DFO-PD-L1 mAb without or with unlabeled avelumab (10, 20, 40, and 400 mu g). Results: [Zr-89]Zr-DFO-PD-L1 mAb exhibited high affinity (K-d similar to 0.3 nM) and detected moderate PD-L1 expression levels in MDA-MB231 cells. The spleen and lymph nodes exhibited the highest [Zr-89]Zr-DFO-PD-L1 mAb uptakes in all time points, while MDA-MB231 tumor uptakes were lower but highly retained. In the unlabeled avelumab dose escalation studies, spleen tissue-muscle ratios decreased in a dose-dependent manner indicating specific [Zr-89]Zr-DFO-PD-L1 mAb binding to PD-L1. In contrast, lymph node and tumor tissue-muscle ratios increased 4- to 5-fold at 20 and 40 mu g avelumab doses. Conclusions: [Zr-89]Zr-DFO-PD-L1 mAb exhibited specific and high affinity for PD-L1 in vitro and had target tissue uptakes correlating with PD-L1 expression levels in vivo. [Zr-89]Zr-DFO-PD-L1 mAb uptake in PD-L1+tumors increased with escalating doses of avelumab.
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