(구)글로벌 핫이슈
핵의학
- 2015년 08월호
Noninvasive Imaging of Tumor PD-L1 Expression Using Radiolabeled Anti-PD-L1 Antibodies.(Radboud University Medical Center/Sandra Heskamp*)
- 출처
- Cancer Res.
- 등재일
- 2015 Jul 15
- 저널이슈번호
- 75(14):2928-36.
- 내용
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 ((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.
Author Information
Heskamp S1, Hobo W2, Molkenboer-Kuenen JD3, Olive D4, Oyen WJ3, Dolstra H2, Boerman OC3.
1Departments of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands. sandra.heskamp@radboudumc.nl.
2Laboratory Medicine-Laboratory of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands.
3Departments of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
4CRCM, Immunity and Cancer, Inserm, U1068; Institut Paoli-Calmettes; Aix-Marseille Université, UM 105; CNRS, UMR7258, Marseille, France.
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