Radiology and Nuclear Medicine, Radboud University Medical Centre.
July, 2015
Antibodies that block the interaction between programmed death ligand 1 (PD-L1) and PD-1 have shown impressive anti-tumor 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 immunohistochemistry. The optimal antibody dose of 111In-PD-L1.3.1 (Kd = 1 nM) for SPECT/CT imaging was ≤ 1 µg. Highest tumor-to-normal tissue contrast was obtained at day 3 and 7 post injection. 111In-PD-L1.3.1 SPECT/CT showed efficient accumulation in high PD-L1 expressing tumors (MDA-MB-231, SK-Br-3), while no specific uptake was observed in tumors with low or no detectable levels of PD-L1 (SUM149, BT474, 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 non-invasive 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.