Synthesis and evaluation of 177Lu-labeled anti-EGFR Fab antibody for lung cancer

被引:0
作者
Li, Yuan-Yuan [1 ,2 ]
Yu, Jia-Yan [1 ,2 ]
Wang, Tao [1 ,2 ]
Wang, Jing [2 ,3 ]
Zhao, Peng [2 ,3 ]
Yang, Xia [2 ,3 ]
Wei, Hong-Yuan [2 ,4 ]
Chen, Yue [1 ,4 ]
机构
[1] Southwest Med Univ, Dept Nucl Med, Affiliated Hosp, Luzhou 646000, Peoples R China
[2] China Acad Engn Phys, Inst Nucl Phys & Chem, Mianyang 621900, Peoples R China
[3] Lab Targeted Radiopharmaceut Creat, Mianyang 621900, Peoples R China
[4] Key Lab Nucl Med & Mol Imaging Sichuan Prov, Luzhou 646000, Peoples R China
基金
中国国家自然科学基金;
关键词
Fab fragments; Lutetium-177; Anti-EGFR antibody; Biodistribution; Lung cancer; SQUAMOUS-CELL CARCINOMA; TARGETED THERAPY; RADIOIMMUNOTHERAPY; BIODISTRIBUTION; NECK; HEAD;
D O I
10.1007/s10967-025-10030-4
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
Fab fragments obtained via enzymatic digestion of full-length antibodies or by gene recombination technology have smaller molecular weight and greater penetration ability. Those advantages make it uniquely suited to deliver radionuclides. In this study, we prepared a Fab fragment from the anti-EGFR antibody Cetuximab and labeled it with 177Lu. The binding activity in vitro and biodistribution in vivo of [177Lu]Lu-DOTA-Fab-Cetuximab were investigated. The [177Lu]Lu-labeled Fab fragment showed improved tumor penetration and faster blood clearance compared to the full-length antibody.
引用
收藏
页码:2139 / 2149
页数:11
相关论文
共 31 条
  • [1] DeNardo G.L., Concepts in radioimmunotherapy and immunotherapy: radioimmunotherapy from a Lym-1 perspective, Semin Oncol, 32, 1, pp. S27-S35, (2005)
  • [2] Goldenberg D.M., Targeted therapy of cancer with radiolabeled antibodies, J Nucl Med, 43, 5, pp. 693-713, (2002)
  • [3] Shah A., Rauth S., Aithal A., Kaur S., Ganguly K., Orzechowski C., Varshney G.C., Jain M., Batra S.K., The current landscape of antibody-based therapies in solid malignancies, Theranostics, 11, 3, pp. 1493-1512, (2021)
  • [4] Jin S., Sun Y., Liang X., Gu X., Ning J., Xu Y., Chen S., Pan L., Emerging new therapeutic antibody derivatives for cancer treatment, Signal Transduct Target Ther, 7, 1, pp. 638-665, (2022)
  • [5] Bernard-Marty C., Lebrun F., Awada A., Piccart M.J., Monoclonal antibody-based targeted therapy in breast cancer: Current status and future directions, Drugs, 66, 12, pp. 1577-1591, (2006)
  • [6] Savage A.P., Cooke T., Epidermal growth factor receptors, Br J Surg, 72, 9, (1985)
  • [7] Nazmi M.N., Dykes P.J., Marks R., Epidermal growth factor receptors in human epidermal tumours, Br J Dermatol, 123, 2, pp. 153-161, (1990)
  • [8] Chen J., Zeng F., Forrester S.J., Eguchi S., Zhang M.-Z., Harris R.C., Expression and function of the epidermal growth factor receptor in physiology and disease, Physiol Rev, 96, 3, pp. 1025-1069, (2016)
  • [9] Bianco R., Melisi D., Ciardiello F., Tortora G., Key cancer cell signal transduction pathways as therapeutic targets, Eur J Cancer, 42, 3, pp. 290-294, (2006)
  • [10] Levantini E., Maroni G., Del Re M., Tenen D.G., EGFR signaling pathway as therapeutic target in human cancers, Semin Cancer Biol, 85, pp. 253-275, (2022)