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Cancer Immunol Res. 2019 Jan;7(1):150-161. doi: 10.1158/2326-6066.CIR-18-0280. Epub 2018 Nov 20.

PD-L1 microSPECT/CT Imaging for Longitudinal Monitoring of PD-L1 Expression in Syngeneic and Humanized Mouse Models for Cancer.

Author information

1
Department of Radiology and Nuclear Medicine, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands. Sandra.Heskamp@radboudumc.nl.
2
Department of Radiology and Nuclear Medicine, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
3
Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands.
4
CRCM, Immunity and Cancer, Inserm, U1068, Institut Paoli-Calmettes, Aix-Marseille Université, UM 105, CNRS, UMR7258, Marseille, France.
5
Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands.

Abstract

Antibodies that block the interaction between programmed death ligand 1 (PD-L1) and PD-1 have shown impressive responses in subgroups of patients with cancer. PD-L1 expression in tumors seems to be a prerequisite for treatment response. However, PD-L1 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+ 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 micro single-photon emission tomography/computed tomography (microSPECT/CT) using radiolabeled PD-L1 antibodies to (i) measure PD-L1 expression in two immunocompetent tumor models (syngeneic mice and humanized mice harboring PD-L1 expressing immune cells) and (ii) monitor therapy-induced changes in tumor PD-L1 expression. We showed that radiolabeled PD-L1 antibodies accumulated preferentially in PD-L1+ tumors, despite considerable uptake in certain normal lymphoid tissues (spleen and lymph nodes) and nonlymphoid tissues (duodenum and brown fat). PD-L1 microSPECT/CT imaging could also distinguish between high and low PD-L1-expressing tumors. The presence of PD-L1+ immune cells did not compromise tumor uptake of the human PD-L1 antibodies in humanized mice, and we demonstrated that radiotherapy-induced upregulation of PD-L1 expression in murine tumors could be monitored with microSPECT/CT imaging. Together, these data demonstrate that PD-L1 microSPECT/CT is a sensitive technique to detect variations in tumor PD-L1 expression, and in the future, this technique may enable patient selection for PD-1/PD-L1-targeted therapy.

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