Noninvasive Imaging of Tumor PD-L1 Expression Using Radiolabeled Anti-PD-L1 Antibodies

• Published in: Cancer research (Chicago, Ill.) Vol. 75; no. 14; pp. 2928 - 2936
• Main Authors: Heskamp, Sandra, Hobo, Willemijn, Molkenboer-Kuenen, Janneke D M, Olive, Daniel, Oyen, Wim J G, Dolstra, Harry, Boerman, Otto C
• Format: Journal Article
• Language: English
• Published: United States 15.07.2015
• Subjects: Animals; Antibodies, Monoclonal; B7-H1 Antigen - immunology; B7-H1 Antigen - metabolism; Breast Neoplasms - diagnostic imaging; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Female; Heterografts; Humans; Indium Radioisotopes - metabolism; MCF-7 Cells; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Protein Binding; Tissue Distribution; Tomography, Emission-Computed, Single-Photon - methods; Tumor Cells, Cultured
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-14-3477

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 ((111)In) 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 (111)In-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. (111)In-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 (111)In-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. (111)In-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.