用[镓]镓-诺他-Nb109对患者来源的肺癌异种移植瘤中PD-L1表达进行免疫正电子发射断层扫描成像。
Immuno-PET imaging of PD-L1 expression in patient-derived lung cancer xenografts with [Ga]Ga-NOTA-Nb109.
作者信息
Liu Qingzhu, Wang Xiaodan, Yang Yanling, Wang Chao, Zou Jian, Lin Jianguo, Qiu Ling
机构信息
NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, China.
Wuxi Second Hospital Affiliated to Nanjing Medical University, Wuxi, China.
出版信息
Quant Imaging Med Surg. 2022 Jun;12(6):3300-3313. doi: 10.21037/qims-21-991.
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 [Ga]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 biodistribution and metabolism of [Ga]Ga-NOTA-Nb109 were investigated using region of interest (ROI) analysis. The biodistribution of [Ga]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 [Ga]Ga-NOTA-Nb109 can accurately and sensitively assess the PD-L1 expression in non-small cell lung cancer (NSCLC) PDX models. The maximum [Ga]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. and biodistribution analysis showed that [Ga]Ga-NOTA-Nb109 was rapidly cleared through renal excretion and an enhanced signal-to-noise ratio (SNR) was achieved. PD-L1 expression analysis showed good agreement with PET imaging results.
CONCLUSIONS
This study demonstrated that [Ga]Ga-NOTA-Nb109 could be applied with PET imaging to noninvasively and accurately monitor PD-L1 expression for screening patients who may be responsive to immunotherapy and to guide the development of appropriate treatment strategies for such patients.
背景
准确评估癌症患者程序性死亡配体1（PD-L1）的表达水平，可能有助于识别抗程序性死亡-1/PD-L1（抗PD-1/PD-L1）免疫检查点疗法的潜在候选者，以提高免疫检查点阻断疗法的有效率。本研究评估了基于纳米抗体的正电子发射断层扫描（PET）示踪剂[Ga]Ga-NOTA-Nb109在肺癌患者来源的异种移植瘤（PDX）中进行PD-L1免疫PET成像的可行性。
方法
我们构建了2个肺腺癌（ADC）和肺鳞状细胞癌（SCC）的PDX，并将它们用于免疫PET成像。对样本进行了2小时的动态PET扫描，并使用感兴趣区域（ROI）分析研究了[Ga]Ga-NOTA-Nb109的生物分布和代谢情况。通过静态PET扫描研究了[Ga]Ga-NOTA-Nb109在2个PDX中的生物分布。此外，通过放射自显影、蛋白质印迹和免疫组织化学（IHC）分析评估了2个PDX中的肿瘤PD-L1表达。
结果
非侵入性PET成像显示，[Ga]Ga-NOTA-Nb109可以准确、灵敏地评估非小细胞肺癌（NSCLC）PDX模型中的PD-L1表达。注射后20分钟，ADC PDX LU6424和SCC PDX LU6437对[Ga]Ga-NOTA-Nb109的最大摄取量分别为每毫升组织体积3.13%±0.35%和2.60%±0.32%注射剂量（ID/mL）。生物分布分析表明，[Ga]Ga-NOTA-Nb109通过肾脏排泄迅速清除，并实现了增强的信噪比（SNR）。PD-L1表达分析与PET成像结果显示出良好的一致性。
结论
本研究表明，[Ga]Ga-NOTA-Nb109可与PET成像一起用于无创、准确地监测PD-L1表达，以筛选可能对免疫治疗有反应的患者，并指导为此类患者制定合适的治疗策略。
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