Quantitative PET imaging of PD-L1 expression in xenograft and syngeneic tumor models using a site-specifically labelled PD-L1 antibody

Despite remarkable clinical responses and prolonged survival across several cancers, not all patients benefit from PD-1/PD-L1 immune checkpoint blockade. Accordingly, assessment of tumor PD-L1 expression by immunohistochemistry (IHC) is increasingly applied to guide patient selection, therapeutic monitoring, and improve overall response rates. However, tissue-based methods are invasive and prone to sampling error. We therefore developed a PET radiotracer to specifically detect PD-L1 expression in a non-invasive manner, which could be of diagnostic and predictive value.

The imaging specificity of Zr-89 radiolabeled anti-PD-L1 monoclonal antibody (clone 6E11) was evaluated in a panel of non-small cell lung cancer xenograft models and in syngeneic models with different levels of PD-L1 expression. To evaluate the predictive value of 89Zr-DFO-6E11 PET imaging, CT26 tumor-bearing mice were subjected to external radiation therapy (XRT) in combination with PD-L1 blockade.

In the publication we demonstrate specific non-invasive imaging of tumor PD-L1 expression. Futhermore we show that PD-L1 expression can be modulated by external radiotherapy and 89Zr-DFO-6E11 PET is able to monitor these changes and predict the response to therapy in an immunocompetent tumor model. Please see full article to read more.

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