Abstract
1135
Purpose: Recently, various immuno-PET tracers based on monoclonal antibodies (mAbs), engineered scaffold proteins and peptides were developed to target either PD-1 or PD-L1, showing promise in assessment of immune checkpoints. We sought to develop an immunotherapeutic agent-based PET probe that enable real-time assessment of PD-L1 expression and evaluation of antibody drug biodistribution to select eligible candidates for anti-PD-1/PD-L1 immunotherapies.
Methods: KN035, a 79.6 kDa size of anti-PD-L1 domain antibody under analysis in clinical trials was used to develop the immuno-PET probe, 89Zr-Df-KN035. Immuno-PET studies were performed to monitor PD-L1 levels in nude mice bearing LN229 xenografts with positive expression for PD-L1, and to evaluate the whole-body biodistribution in healthy non-human primates (NHPs). Results LN229 xenografts were markedly visualized from 24 h after injection of 89Zr-Df-KN035, with elevated accumulation persisting for up to 120 h. Tumor radioactivity was notably reduced in the presence of excess KN035. Mouse ex vivo biodistribution studies performed at 24 h and 120 h revealed tumor-to-muscle ratios as high as 5.64 ± 0.65 and 7.70 ± 1.37, respectively. In the NHP model, PET imaging demonstrated low background. The liver and kidney showed moderate accumulation with the highest SUVmean value of 1.15 ± 0.15 and 2.13 ± 0.10 at 72 h, respectively. The spleen, lymph nodes and salivary glands were also slightly visualized.
Conclusions: 89Zr-Df-KN035, a novel anti-PD-L1 domain antibody-based probe shows the feasibility of non-invasive in vivo evaluation of PD-L1 expression. This work further provides a template for immunotherapeutic agent-based imaging to evaluate human PD-L1 expression and to augment our understanding of therapeutic agent biodistribution, leading to better therapeutic strategies in the future. Keywords: PD-L1; domain antibody; 89Zr; immuno-PET imaging