Qingzhu Liu1, Xiaodan Wang2, Yanling Yang3, Chao Wang3, Jian Zou4, Jianguo Lin1,5, Ling Qiu1,5. 1. NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, China. 2. Wuxi Second Hospital Affiliated to Nanjing Medical University, Wuxi, China. 3. Suzhou Smart Nuclide Biopharmaceutical Co. Ltd., Suzhou Industrial Park, Suzhou, China. 4. Center of Clinical Research, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China. 5. Department of Radiopharmaceuticals, School of Pharmacy, Nanjing Medical University, Nanjing, China.
Abstract
Background: Accurate evaluation of programmed death-ligand 1 (PD-L1) expression levels in cancer patients may be useful in the identification of potential candidates for anti-programmed death-1/PD-L1 (anti-PD-1/PD-L1) immune checkpoint therapy to improve the response rate of immune checkpoint blockade therapy. This study evaluated the feasibility of the nanobody-based positron emission tomography (PET) tracer [68Ga]Ga-NOTA-Nb109 for immuno-PET imaging of PD-L1 in lung cancer patient-derived xenograft (PDX). Methods: We constructed 2 PDXs of lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SCC) and used them for immuno-PET imaging. A 2-hour dynamic PET scanning was performed on the samples and the in vivo biodistribution and metabolism of [68Ga]Ga-NOTA-Nb109 were investigated using region of interest (ROI) analysis. The ex vivo biodistribution of [68Ga]Ga-NOTA-Nb109 in the 2 PDXs was investigated by static PET scanning. In addition, tumor PD-L1 expression in the 2 PDXs was evaluated by autoradiography, western blot, and immunohistochemical (IHC) analysis. Results: Noninvasive PET imaging showed that [68Ga]Ga-NOTA-Nb109 can accurately and sensitively assess the PD-L1 expression in non-small cell lung cancer (NSCLC) PDX models. The maximum [68Ga]Ga-NOTA-Nb109 uptake by the ADC PDX LU6424 and the SCC PDX LU6437 were 3.13%±0.35% and 2.60%±0.32% injected dose per milliliter of tissue volume (ID/mL), respectively, at 20 min post injection. In vivo and ex vivo biodistribution analysis showed that [68Ga]Ga-NOTA-Nb109 was rapidly cleared through renal excretion and an enhanced signal-to-noise ratio (SNR) was achieved. Ex vivo PD-L1 expression analysis showed good agreement with in vivo PET imaging results. Conclusions: This study demonstrated that [68Ga]Ga-NOTA-Nb109 could be applied with PET imaging to noninvasively and accurately monitor PD-L1 expression in vivo for screening patients who may be responsive to immunotherapy and to guide the development of appropriate treatment strategies for such patients. 2022 Quantitative Imaging in Medicine and Surgery. All rights reserved.
Background: Accurate evaluation of programmed death-ligand 1 (PD-L1) expression levels in cancer patients may be useful in the identification of potential candidates for anti-programmed death-1/PD-L1 (anti-PD-1/PD-L1) immune checkpoint therapy to improve the response rate of immune checkpoint blockade therapy. This study evaluated the feasibility of the nanobody-based positron emission tomography (PET) tracer [68Ga]Ga-NOTA-Nb109 for immuno-PET imaging of PD-L1 in lung cancer patient-derived xenograft (PDX). Methods: We constructed 2 PDXs of lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SCC) and used them for immuno-PET imaging. A 2-hour dynamic PET scanning was performed on the samples and the in vivo biodistribution and metabolism of [68Ga]Ga-NOTA-Nb109 were investigated using region of interest (ROI) analysis. The ex vivo biodistribution of [68Ga]Ga-NOTA-Nb109 in the 2 PDXs was investigated by static PET scanning. In addition, tumor PD-L1 expression in the 2 PDXs was evaluated by autoradiography, western blot, and immunohistochemical (IHC) analysis. Results: Noninvasive PET imaging showed that [68Ga]Ga-NOTA-Nb109 can accurately and sensitively assess the PD-L1 expression in non-small cell lung cancer (NSCLC) PDX models. The maximum [68Ga]Ga-NOTA-Nb109 uptake by the ADC PDX LU6424 and the SCC PDX LU6437 were 3.13%±0.35% and 2.60%±0.32% injected dose per milliliter of tissue volume (ID/mL), respectively, at 20 min post injection. In vivo and ex vivo biodistribution analysis showed that [68Ga]Ga-NOTA-Nb109 was rapidly cleared through renal excretion and an enhanced signal-to-noise ratio (SNR) was achieved. Ex vivo PD-L1 expression analysis showed good agreement with in vivo PET imaging results. Conclusions: This study demonstrated that [68Ga]Ga-NOTA-Nb109 could be applied with PET imaging to noninvasively and accurately monitor PD-L1 expression in vivo for screening patients who may be responsive to immunotherapy and to guide the development of appropriate treatment strategies for such patients. 2022 Quantitative Imaging in Medicine and Surgery. All rights reserved.
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