Antibodies that block the interaction between programmed death ligand 1 (PD-L1) and PD-1 have shown impressive responses in subgroups of cancer patient. PD-L1 expression in the tumor seems to be a pre-requisite for treatment response. However, it is heterogeneously expressed within tumor lesions and may change upon disease progression and treatment. Imaging of PD-L1 could aid in patient selection.
Previously, we showed the feasibility to image PD-L1 positive tumors in immunodeficient mice. However, PD-L1 is also expressed on immune cell subsets. Therefore, the aim of this study was to assess the potential of PD-L1 microSPECT/CT using radiolabeled anti-PD-L1 antibodies to 1) measure PD-L1 expression in two immunocompetent tumor models (syngeneic mice and humanized mice harboring PD-L1 expressing immune cells) and 2) monitor therapy induced changes in tumor PD-L1 expression levels.
We showed that radiolabeled anti-PD-L1 antibodies accumulated preferentially in PD-L1 positive tumors, despite considerable uptake in certain normal lymphoid tissues (spleen and lymph nodes) and non-lymphoid tissues (duodenum and brown fat). Moreover, PD-L1 microSPECT/CT imaging could distinguish between high and low PD-L1 expressing tumors. Notably, presence of PD-L1 positive immune cells did not compromise tumor uptake of the anti-human PD-L1 antibodies in humanized mice. Most importantly, we demonstrated that radiotherapy induced up-regulation of PD-L1 expression in murine tumors which could be monitored with microSPECT/CT imaging.
Together, these data demonstrate that PD-L1 microSPECT/CT is a sensitive technique to detect varying levels of tumor PD-L1 expression and in the future, this technique may enable patient selection for PD-1/PD-L1 targeted therapy.
Radboud UMC.
Netherlands Organisation for Scientific Research and Dutch Cancer Society.
All authors have declared no conflicts of interest.