Non-invasive PD-L1 quantification using [18F]DK222-PET imaging in cancer immunotherapy

作者：Akhilesh C. Mishra, Kuldeep Gupta, Dhiraj Kumar, Gabriela Lofland, Ajay Sharma, Lilja B. Sólnes, Steven P. Rowe, Patrick M. Forde, Martin G. Pomper, Edward W. Gabrielson, Sridhar Nimmagadda · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2023 · DOI：10.1136/jitc-2023-007535 · 被引用次数：24 · 研究领域：Cancer Immunotherapy and Biomarkers、Medical Imaging Techniques and Applications、Cancer Genomics and Diagnostics

Background Combination therapies that aim to improve the clinical efficacy to immune checkpoint inhibitors have led to the need for non-invasive and early pharmacodynamic biomarkers. Positron emission tomography (PET) is a promising non-invasive approach to monitoring target dynamics, and programmed death-ligand 1 (PD-L1) expression is a central component in cancer immunotherapy strategies. [18F]DK222, a peptide-based PD-L1 imaging agent, was investigated in this study using humanized mouse models to explore the relationship between PD-L1 expression and therapy-induced changes in cancer. Methods Cell lines and xenografts derived from three non-small cell lung cancers (NSCLCs) and three urothelial carcinomas (UCs) were used to validate the specificity of [18F]DK222 for PD-L1. PET was used to quantify anti-programmed cell death protein-1 (PD-1) therapy-induced changes in PD-L1 expression in tumors with and without microsatellite instability (MSI) in humanized mice. Furthermore, [18F]DK222-PET was used to validate PD-L1 pharmacodynamics in the context of monotherapy and combination immunotherapy in humanized mice bearing A375 melanoma xenografts. PET measures of PD-L1 expression were used to establish a relationship between pathological and immunological changes. Lastly, spatial distribution analysis of [18F]DK222-PET was developed to assess the effects of different immunotherapy regimens on tumor heterogeneity. Results [18F]DK222-PET and biodistribution studies in mice with NSC...