<sup>99m </sup>Tc-Labeled PD-L1 nanobody for SPECT/CT imaging of non-small cell lung cancer

ZHAO Lingzhou; XING Yan; LIU Changcun; GUO Lilei; QIAO Wenli; ZHAO Jinhua

doi:10.19732/j.cnki.2096-6210.2019.04.002

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^99mTc-Labeled PD-L1 nanobody for SPECT/CT imaging of non-small cell lung cancer

更新时间：2025-12-15

- ^99mTc-Labeled PD-L1 nanobody for SPECT/CT imaging of non-small cell lung cancer
- Vol. 28, Issue 4, Pages: 216-222(2019)
- 作者机构：
- 作者简介：
- 基金信息：
- DOI：10.19732/j.cnki.2096-6210.2019.04.002
  CLC：
- Published Online：12 September 2019，
  
  Published：12 September 2019
- 稿件说明：
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赵凌舟,邢岩,刘长存,等. ⁹⁹m Tc标记PD-L1纳米抗体用于荷非小细胞肺癌模型SPECT/CT显像[J]. 肿瘤影像学, 2019, 28(4): 216-222 https://doi.

org/10.19732/j.cnki.2096-6210.2019.04.002
赵凌舟,邢岩,刘长存,等. ⁹⁹m Tc标记PD-L1纳米抗体用于荷非小细胞肺癌模型SPECT/CT显像[J]. 肿瘤影像学, 2019, 28(4): 216-222 https://doi. DOI： 10.19732/j.cnki.2096-6210.2019.04.002.

org/10.19732/j.cnki.2096-6210.2019.04.002 DOI：

摘要

目的：

使用放射性核素

99m

Tc标记程序性死亡受体-配体1（programmed cell death-ligand 1，PD-L1）纳米抗体，制备靶向非小细胞肺癌（non-small cell lung cancer，NSCLC）的显像剂（

99m

Tc-PD-L1纳米抗体），评价其在SPECT/CT上显示肿瘤PD-L1表达的可行性。

方法：

采用三羰基化合物试剂盒制备标记前体三羰基锝化合物盐溶液，标记PD-L1纳米抗体，并测定标志物的标记率、放射化学纯度及体外稳定性；分别构建PD-L1高表达（HCC827）和PD-L1阴性（A549）的 NSCLC裸鼠移植瘤模型，经尾静脉注射

99m

Tc-PD-L1纳米抗体30、90 min后，观察和分析SPECT/CT显像。

结果：

99m

Tc-PD-L1纳米抗体的标记率在95%以上，且在磷酸盐缓冲液（phosphate buffered saline，PBS）和血清中均表现良好的稳定性。小动物SPECT/CT显像表明

99m

Tc-PD-L1纳米抗体在PD-L1高表达组中具有良好的肿瘤摄取，而在PD-L1阴性组无明显肿瘤摄取，表明

99m

Tc-PD-L1纳米抗体能够显示肿瘤PD-L1的表达情况，具有良好的体内特异性；此外，

99m

Tc-PD-L1纳米抗体主要分布在肾脏，通过泌尿系统排泄，肝脏、脾脏、心脏、肺及软组织等显影微弱，甲状腺区及胃肠未见核素浓聚，证实显像剂具有良好的生物分布。

结论：

该研究利用三羰基化合物试剂盒成功制备了

99m

Tc-PD-L1纳米抗体，标志物具有良好的标记率和体外稳定性，能够在PD-L1高表达NSCLC中特异性浓聚，有潜力成为一种新型的显示肿瘤PD-L1表达的显像剂。

Abstract

Objective:

In this study

99m

Tc-labeled PD-L1 nanobody was prepared and its potential as a SPECT/CT imaging agentfor the visualization of tumor PD-L1 ex

pression was performed via a xenograft nude mouse model.

Methods:

The PD-L1 nanobody was radiolabeled with

99m

Tc(CO) 3 (H 2 O) 3 . The radiolabeling yields and stabilities were studied by radio-active instant thin layer chromatography (radio-ITLC) and high performance liquid chromatography (HPLC). Micro-SPECT/CT imaging was performed at 30

90 min after intravenous injection of

99m

Tc-PD-L1 nanobody in HCC827 and A549 as PD-L1 expression positive and negative groups

respectively.

Results:

The radiochemical yield of

99m

Tc-PD-L1 nanobody was above 95%

and was stable within 3 h both in phosphate buffered saline (PBS) and human serum at 37℃. SPECT images of 99m Tc-PD-L1 nanobody in tumor models showed that HCC827 tumor lesions were visualized with high contrast at 30

90 min post-injection

while no obvious radioactive signal could be found in A549 tumor lesions

suggesting that the formed

99m

Tc-PD-L1 nanobody could show the PD-L1 expression in tumors and had favorable specificity invivo. Moreover

the

99m

Tc-PD-L1 was mainly accumulated in kidneys and eliminated from the body through urinary system

while other tissues

including liver

spleen

heart

lung and soft tissues

displayed low accumulation and no obvious radioactivity was found in thyroid and gastrointestinal system

indicating the beneficial biodistribution of

99m

Tc-PD-L1.

Conclusion:

99m

Tc-PD-L1 nanobody was successfully prepared with a high radiochemical purity and stability

and could be used as a tumor- specific ligand for SPECT imaging of tumor PD-L1 expression.

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Related Institution

Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals, National Medical Products Administration, Beijing Key Laboratory of Carcinogenesis and Translational Research

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Guizhou University Medicine College

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99m Tc-Labeled PD-L1 nanobody for SPECT/CT imaging of non-small cell lung cancer

DOI：10.19732/j.cnki.2096-6210.2019.04.002

摘要

Abstract

关键词

Keywords

references

^99mTc-Labeled PD-L1 nanobody for SPECT/CT imaging of non-small cell lung cancer