Preparation and application of a PDGFRβ-targeted near-infrared fluorescent probe for molecular optical imaging of lung cancer_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

FAN Jie , TAO Ze , LI Heng , YANG Fen , YANG Hao ,  LU Xiaofeng

Key Lab of Transplant Engineering and Immunology, National Health Commission of the People's Republic of China, West China Hospital, Sichuan University, Chengdu, 610041, P.R.China;

Corresponding author：

LU Xiaofeng, Email: xiaofenglu@scu.edu.cn

Keywords：

Lung cancer; optical imaging; molecular probe; affibody; platelet-derived growth factor receptor

DOI：

10.7507/1007-4848.202104050

Video：

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Objective To prepare platelet-derived growth factor receptor β (PDGFRβ)-targeted near-infrared molecular probe and evaluate its potential in optical molecular imaging of lung cancer.Methods PDGFRβ-specific affibody Z-tri was recombinantly expressed in Escherichia coli (E. coli) and purified using affinity chromatography. In vitro cell-binding of Z-tri was analyzed by flow cytometry. Cellular distribution of Z-tri in tumor grafts was determined by protein-tracing. The molecular probe ^CF750-Z-tri was prepared by conjugating near-infrared fluorescent dye CF750 to Z-tri. The optical images of xenografts of lung cancer were obtained by using ^CF750-Z-tri combined with optical imaging system.Results PDGFRβ-specific affibody Z-tri was highly expressed in E. coli and purified to homogeneity. Z-tri could bind PDGFRβ-positive cells but not PDGFRβ-negative cells cultured in vitro. In the tumor xenografts of human lung cancer, intravenously injected Z-tri was predominantly distributed on cells overexpressing PDGFRβ. The near infrared fluorescent dye CF750 was efficiently conjugated to Z-tri. Optical images with high contrast of lung cancer xenografts were produced by using the near-infrared fluorescent probe ^CF750-Z-tri combined with optical imaging system.Conclusion The near-infrared fluorescent probe ^CF750-Z-tri can be used for optical imaging of human lung cancer, which takes great potential in optical imaging-guided surgery of lung cancer.

Citation： FAN Jie, TAO Ze, LI Heng, YANG Fen, YANG Hao, LU Xiaofeng. Preparation and application of a PDGFRβ-targeted near-infrared fluorescent probe for molecular optical imaging of lung cancer. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2021, 28(7): 841-848. doi: 10.7507/1007-4848.202104050 Copy

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26.	Low PS, Singhal S, Srinivasarao M. Fluorescence-guided surgery of cancer: Applications, tools and perspectives. Curr Opin Chem Biol, 2018, 45: 64-72.
27.	梁伟俊, 吴德庆, 吕泽坚, 等. 吲哚菁绿荧光直肠镜在直肠癌手术中的应用. 中华胃肠外科杂志, 2020, 23(11): 1104-1105.
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30.	吴纯威, 黄晓新, 金观桥, 等. 表皮生长因子受体靶向治疗分子影像研究进展. 中国医学影像技术, 2020, 36(5): 767-771.
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1. Jiang HY, Chen J, Xia CC, et al. Noninvasive imaging of hepatocellular carcinoma: From diagnosis to prognosis. World J Gastroenterol, 2018, 24(22): 2348-2362.
2. Inage T, Nakajima T, Yoshino I, et al. Early lung cancer detection. Clin Chest Med, 2018, 39(1): 45-55.
3. Wang C, Wang Z, Zhao T, et al. Optical molecular imaging for tumor detection and image-guided surgery. Biomaterials, 2018, 157: 62-75.
4. 王燕, 方向明. 光学分子影像导航下精准手术的应用与研究进展. 医学综述, 2020, 26(3): 571-576.
5. de Vries EGE, Kist de Ruijter L, Lub-de Hooge MN, et al. Integrating molecular nuclear imaging in clinical research to improve anticancer therapy. Nat Rev Clin Oncol, 2019, 16(4): 241-255.
6. Liang Q, Kong L, Zhu X, et al. Noninvasive imaging for assessment of the efficacy of therapeutic agents for hepatocellular carcinoma. Mol Imaging Biol, 2020, 22(6): 1455-1468.
7. 吴睿, 卢久富, 郝亮, 等. 分子影像探针. 化学通报, 2019, 82: 886-892.
8. Pirovano G, Roberts S, Kossatz S, et al. Optical imaging modalities: Principles and applications in preclinical research and clinical settings. J Nucl Med, 2020, 61(10): 1419-1427.
9. Rogalla S, Joosten SCM, Alam IS, et al. Intraoperative molecular imaging in lung cancer: The state of the art and the future. Mol Ther, 2018, 26(2): 338-341.
10. 迟崇巍, 叶津佐, 王坤, 等. 术中精准医学诊疗方法--光学分子影像手术导航技术. 生物产业技术, 2014, 24: 7-11.
11. Zhou Z, Lu ZR. Molecular imaging of the tumor microenvironment. Adv Drug Deliv Rev, 2017, 113: 24-48.
12. Joshi BP, Wang TD. Targeted optical imaging agents in cancer: Focus on clinical applications. Contrast Media Mol Imaging, 2018, 2018: 2015237.
13. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
14. Keating JJ, Runge JJ, Singhal S, et al. Intraoperative near-infrared fluorescence imaging targeting folate receptors identifies lung cancer in a large-animal model. Cancer, 2017, 123(6): 1051-1060.
15. Kennedy GT, Okusanya OT, Keating JJ, et al. The optical biopsy: A novel technique for rapid intraoperative diagnosis of primary pulmonary adenocarcinomas. Ann Surg, 2015, 262(4): 602-609.
16. Keating JJ, Okusanya OT, De Jesus E, et al. Intraoperative molecular imaging of lung adenocarcinoma can identify residual tumor cells at the surgical margins. Mol Imaging Biol, 2016, 18(2): 209-218.
17. Liu J, Liu C, Qiu L, et al. Overexpression of both platelet-derived growth factor-BB and vascular endothelial growth factor-C and its association with lymphangiogenesis in primary human non-small cell lung cancer. Diagn Pathol, 2014, 9: 128.
18. Kanzaki R, Ose N, Kawamura T, et al. Stromal PDGFR-β expression is associated with postoperative survival of non-small cell lung cancer patients receiving preoperative chemo- or chemoradiotherapy followed by surgery. World J Surg, 2018, 42(9): 2879-2886.
19. Kilvaer TK, Rakaee M, Hellevik T, et al. Differential prognostic impact of platelet-derived growth factor receptor expression in NSCLC. Sci Rep, 2019, 9(1): 10163.
20. Lindborg M, Cortez E, Höidén-Guthenberg I, et al. Engineered high-affinity affibody molecules targeting platelet-derived growth factor receptor β in vivo. J Mol Biol, 2011, 407(2): 298-315.
21. Wirz JA, Boudko SP, Lerch TF, et al. Crystal structure of the human collagen XV trimerization domain: A potent trimerizing unit common to multiplexin collagens. Matrix Biol, 2011, 30(1): 9-15.
22. Fan Q, Cai H, Yang H, et al. Biological evaluation of 131I- and CF750-labeled Dmab(scFv)-Fc antibodies for xenograft imaging of CD25-positive tumors. Biomed Res Int, 2014, 2014: 459676.
23. Povoski SP, Neff RL, Mojzisik CM, et al. A comprehensive overview of radioguided surgery using gamma detection probe technology. World J Surg Oncol, 2009, 7: 11.
24. Predina JD, Newton AD, Keating J, et al. Intraoperative molecular imaging combined with positron emission tomography improves surgical management of peripheral malignant pulmonary nodules. Ann Surg, 2017, 266(3): 479-488.
25. Nakaseko Y, Ishizawa T, Saiura A. Fluorescence-guided surgery for liver tumors. J Surg Oncol, 2018, 118(2): 324-331.
26. Low PS, Singhal S, Srinivasarao M. Fluorescence-guided surgery of cancer: Applications, tools and perspectives. Curr Opin Chem Biol, 2018, 45: 64-72.
27. 梁伟俊, 吴德庆, 吕泽坚, 等. 吲哚菁绿荧光直肠镜在直肠癌手术中的应用. 中华胃肠外科杂志, 2020, 23(11): 1104-1105.
28. Wang P, Fan Y, Lu L, et al. NIR-Ⅱ nanoprobes in-vivo assembly to improve image-guided surgery for metastatic ovarian cancer. Nat Commun, 2018, 9(1): 2898.
29. Tao Z, Yang H, Shi Q, et al. Targeted delivery to tumor-associated pericytes via an affibody with high affinity for PDGFRβ enhances the in vivo antitumor effects of human TRAIL. Theranostics, 2017, 7(8): 2261-2276.
30. 吴纯威, 黄晓新, 金观桥, 等. 表皮生长因子受体靶向治疗分子影像研究进展. 中国医学影像技术, 2020, 36(5): 767-771.
31. Tolmachev V, Orlova A. Affibody molecules as targeting vectors for PET imaging. Cancers (Basel), 2020, 12(3): 651.

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Preparation and application of a PDGFRβ-targeted near-infrared fluorescent probe for molecular optical imaging of lung cancer

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