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作者

Xu Yang, Jun Liu, Cuicui Li, Lingling Zheng, Xia Lu, Ziang Zhou, Xianyu Zhu, Jianhua Gong, Qingfang Miao, Jigang Yang

作者单位

Affiliations ¹ Department of Nuclear Medicine, Beijing Friendship Hospital, Capital Medical University, 95 Yong An Road, Xi Cheng District, Beijing, 100050, China. ² Department of PET-CT Centre, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China. ³ NHC Key Laboratory of Biotechnology of Antibiotic, Department of Oncology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College,, Courtyard No. 2, Nanwei Rd., Xicheng Dist, Beijing, 100050, China. ann_gong@imb.pumc.edu.cn. ⁴ NHC Key Laboratory of Biotechnology of Antibiotic, Department of Oncology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College,, Courtyard No. 2, Nanwei Rd., Xicheng Dist, Beijing, 100050, China. miaoqf@imb.pumc.edu.cn. ⁵ Department of Nuclear Medicine, Beijing Friendship Hospital, Capital Medical University, 95 Yong An Road, Xi Cheng District, Beijing, 100050, China. yangjigang@ccmu.edu.cn.

刊名

European journal of nuclear medicine and molecular imaging

年份

2024

ISSN

1619-7089

关键词

CD30 Copper-64 Immuno-PET Letetium-177 Lymphoma Radioimmunotherapy Theranostic.

摘要

Purpose: CD30 serves as an ideal therapeutic target for lymphoma, but its variable expression and high relapse rate pose challenges in targeted therapy. This study aims to label the anti-CD30 monoclonal antibody with Cu/Lu for immuno-positron emission tomography and radioimmunotherapy . Methods: CD30 binding kinetics of anti-CD30-IgG were measured by Biolayer interferometry . Western blotting screened lymphoma cell lines for CD30 expression. Flow cytometry and immunofluorescence validated the ...更多

Purpose: CD30 serves as an ideal therapeutic target for lymphoma, but its variable expression and high relapse rate pose challenges in targeted therapy. This study aims to label the anti-CD30 monoclonal antibody with Cu/Lu for immuno-positron emission tomography and radioimmunotherapy . Methods: CD30 binding kinetics of anti-CD30-IgG were measured by Biolayer interferometry . Western blotting screened lymphoma cell lines for CD30 expression. Flow cytometry and immunofluorescence validated the specific binding of IMB16. IMB16 was conjugated to p-SCN-Bn-NOTA and p-SCN-Bn-DOTA for radiolabeling with Cu and Lu. [Cu]Cu-NOTA-IMB16 and [Lu]Lu-DOTA-IMB16 were used for immuno-PET and RIT in subcutaneous lymphoma NSG mouse models. Results: IMB16 had a strong binding affinity to CD30 according to the BLI. Western blotting revealed high CD30 expression in Karpas299 cells and negative expression in Raji cells. Flow cytometry and immunofluorescence confirmed specific binding of IMB16 to CD30 on cell surface. Radiochemical purity of [Cu]Cu-NOTA-IMB16 and [Lu]Lu-DOTA-IMB16 exceeded 95%. In Immuno-PET imaging, CD30-positive Karpas299 tumours had a mean uptake value of 19.2 ± 0.9%ID/g at 24 h post-injection, significantly higher than Karpas299-blocked and Raji-negative groups at 10 days post-injection, compared to controls. Ex vivo biodistribution and histological staining supported in vivo PET imaging and RIT results. Conclusions: Labelling IMB16 with Cu enabled non-invasive assessment of CD30 expression, while Lu labelling effectively suppressed tumour growth in CD30-positive lymphoma. CD30-targeted theranostic show promise for patient stratification and treatment enhancement, warranting further clinical evaluation.收起

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