Immuno-PET imaging of PD-L1 expression in patient-derived lung cancer xenografts with [ 68 Ga]Ga-NOTA-Nb109

Quantitative Imaging in Medicine and Surgery

article

Qingzhu Liu¹  Xiaodan Wang²  Yanling Yang³  Chao Wang³  Jian Zou⁴  Jianguo Lin¹  Ling Qiu¹ 

[1] NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine , Jiangsu Institute of Nuclear Medicine;Wuxi Second Hospital Affiliated to Nanjing Medical University;Suzhou Smart Nuclide Biopharmaceutical Co. Ltd.;Center of Clinical Research , The Affiliated Wuxi People’s Hospital of Nanjing Medical University;Department of Radiopharmaceuticals, School of Pharmacy , Nanjing Medical University

关键词: PD-L1 expression;    lung cancer;    immuno-PET imaging;    patient-derived xenograft (PDX);    immunotherapy;   

DOI  :  10.21037/qims-21-991

学科分类：外科医学

来源: AME Publications

【 摘 要 】

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.

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