Noninvasive imaging of tumor PD-L1 expression using radiolabeled anti–PD-L1 antibodies

S Heskamp, W Hobo, JDM Molkenboer-Kuenen… - Cancer research, 2015 - AACR
S Heskamp, W Hobo, JDM Molkenboer-Kuenen, D Olive, WJG Oyen, H Dolstra…
Cancer research, 2015AACR
Antibodies that block the interaction between programmed death ligand 1 (PD-L1) and PD-1
have shown impressive antitumor activity. Patients with tumors expressing PD-L1 are most
likely to respond to this treatment. The aim of our study was to develop a noninvasive
imaging technique to determine tumor PD-L1 expression in vivo. This could allow selection
of patients that are most likely to benefit from anti–PD-1/PD-L1 treatment and to monitor PD-
L1 expression during therapy. The monoclonal antibody PD-L1. 3.1 was radiolabeled with …
Abstract
Antibodies that block the interaction between programmed death ligand 1 (PD-L1) and PD-1 have shown impressive antitumor activity. Patients with tumors expressing PD-L1 are most likely to respond to this treatment. The aim of our study was to develop a noninvasive imaging technique to determine tumor PD-L1 expression in vivo. This could allow selection of patients that are most likely to benefit from anti–PD-1/PD-L1 treatment and to monitor PD-L1 expression during therapy. The monoclonal antibody PD-L1.3.1 was radiolabeled with Indium-111 (111In) and characterized using PD-L1–expressing MDA-MB-231 cells. Subsequently, the optimal antibody dose and time point for imaging was determined in mice with MDA-MB-231 xenografts. Finally, SPECT/CT imaging was performed in xenograft models with different PD-L1 expression levels and tumor sections were analyzed for PD-L1 expression using IHC. The optimal antibody dose of 111In-PD-L1.3.1 (Kd = 1 nmol/L) for SPECT/CT imaging was ≤1 μg. Highest tumor-to-normal tissue contrast was obtained at days 3 and 7 after injection. 111In-PD-L1.3.1 SPECT/CT showed efficient accumulation in high PD-L1–expressing tumors (MDA-MB-231 and SK-Br-3), whereas no specific uptake was observed in tumors with low or no detectable levels of PD-L1 (SUM149, BT474, and MCF-7). SPECT/CT and autoradiography showed a very heterogeneous distribution of 111In-PD-L1.3.1 within the tumor. In conclusion, this is the first study showing the feasibility of noninvasive in vivo imaging of PD-L1 expression in tumors. 111In-PD-L1.3.1 showed efficient and specific uptake in PD-L1 expressing xenografts. This technique may enable patient selection for PD-1 and PD-L1–targeted therapy. Cancer Res; 75(14); 2928–36. ©2015 AACR.
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