GlyCLICK PET-tracers in Quantitative Imaging to Predict Immunotherapy Response
Scientists at Minerva Imaging demonstrate the potential of site-specific immuno-PET tracers as early identifiers of immune response activation using in vivo imaging.
The programmed cell death protein (PD-1) on immune cells and its corresponding tumor-associated ligand (PD-L1) have emerged as effective targets for immunocheckpoint therapy. To date, the selection of patients eligible for PD-L1 blockade therapy and response rate monitoring is guided by immunohistochemistry of randomly sampled biopsies. This method is not only invasive and prone to errors, but also poorly reflects the heterogeneity and potential metastasis of the tumor.
Immunoimaging using PET-tracers is an attractive option to overcome these challenges since it provides a more comprehensive portrayal of the tumor and its temporal dynamics in vivo. In this study, Christensen et al. developed a site-specifically labeled immuno-PET tracer using a GlyCLICK-conjugated anti-PD-L1 antibody. The PET-tracer was used for quantitative detection of PD-L1 expression in order to non-invasively monitor radiotherapy-induced changes and demonstrate the predictive value of such tracers prior to PD-L1 blockade immunotherapy.
The anti-PD-L1 antibody was site-specifically conjugated with DIBO-functionalized DFO chelators using the GlyCLICK technology. Chelated conjugates were then radiolabeled with 89Zr to generate PET-tracers carrying two radioisotopes per antibody (DOL=2). Comparing conjugation strategies, the authors found that the GlyCLICK-conjugated antibodies displayed higher immuno-reactivity, stability and affinity compared to random conjugates. In vivo PET imaging and ex vivo biodistribution showed clear PD-L1-specificity of the GlyCLICK-tracers that allowed for the detection of different PD-L1 expression levels among mouse models of human and murine cancer. Importantly, the authors were also able to monitor therapy-induced changes of syngenetic mouse models in a combination study using XRT and anti-PD-L1 therapy. The tumor-to-muscle ratio of GlyCLICK-tracers enabled the scientists to obtain results predictive of response to PD-L1 immunocheckpoint inhibition.
Learn more about how GlyCLICK works by watching the GlyCLICK Movie.
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