Imaging of programmed cell death ligand 1: Impact of protein concentration on distribution of anti-PD-L1 SPECT agents in an immunocompetent murine model of melanoma

Abstract

Programmed cell death ligand 1 (PD-L1) is part of an immune checkpoint system that is essential for preventing autoimmunity and cancer. Recent approaches in immunotherapy that target immune checkpoints have shown great promise in a variety of cancers, including metastatic melanoma. The use of targeted molecular imaging would help identify patients who will best respond to anti-PD-L1 treatment while potentially providing key information to limit immune-related adverse effects. Recently, we developed an antibody-based PD-L1-targeted SPECT agent-111In-diethylenetriaminepentaacetic acid (DTPA)-anti-PD-L1-to identify PD-L1-positive tumors in vivo. To best use such PD-L1-targeted imaging agents, it is important, as a first step, to understand how the signal is affected by different parameters. Methods: We evaluated the impact of protein concentration on the distribution of 111In-DTPA-anti-PD-L1 in a murine model of aggressive melanoma. Results: 111In-DTPA-anti-PD-L1 (dissociation constant, 0.6 6 0.1 nM) demonstrated increased uptake in B16F10 tumors at protein concentrations equaling or exceeding 1 mg/kg at 24 h and 3 mg/kg at 72 h. At 24 h, the PD-L1-rich spleen and lungs demonstrated decreasing uptake with increasing protein concentration. At 72 h, uptake in the thymus was significantly increased at protein concentrations of 3 mg/kg or greater. Both time points demonstrated increased tracer amounts remaining in circulation as the amount of cold antibody was increased. Conclusion: These studies demonstrate that 111In-DTPA-anti-PD-L1 is capable of identifying tumors that overexpresses PD-L1 and monitoring the impact of PD-L1-rich organs on the distribution of anti-PD-L1 antibodies.