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 targeting 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 (irAEs). Recently, we developed an antibody based PD-L1-targeted imaging agent to identify PD-L1 positive tumors in vivo. To further understand how to best use these new 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-BC, an 111In-antibody conjugate targeted to PD-L1, in an aggressive mouse melanoma model. Results: 111In-DTPA-anti-PD-L1 (Kd=0.6±0.1 nM) demonstrated increased uptake in the B16F10 tumor at protein concentrations ≥ 1 mg/kg at 24 hrs and ≥ 3 mg/kg at 72 hrs. At 24 hrs the PD-L1 rich spleen and lungs demonstrated decreasing uptake with increasing protein concentration. At 72 hrs uptake in the thymus was significantly increased at protein concentrations ≥ 3mg/kg. Both time points demonstrated increased tracer amounts remaining in circulation as the amount of cold antibody was introduced. Conclusion: These studies demonstrate that 111In-DTPA-anti-PD-L1 is capable of identifying tumors that overexpresses PD-L1, as well as monitor the impact of PD-L1 rich organs on the distribution of anti-PD-L1 antibodies.
- Animal Imaging
- Molecular Imaging
- SPECT
- SPECT
- anti-PD-L1
- immune checkpoint inhibitors
- melanoma
- targeted antibodies
- Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.