On the shoulder of ADC: The development of 124 I-IMMU-132, an iodine-124-labelled Trop-2-targeting molecular probe for micro-PET imaging.

Autor: Zeng Z; Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China. Electronic address: z66zq@126.com., Zheng Y; Department of Proctology, Wuhan Traditional Chinese Medicine Hospital, Wuhan City, Hubei Province, China. Electronic address: 56834927@qq.com., Yan X; Department of Genitourinary Oncology, Peking University Cancer Hospital & Institute, Beijing, China. Electronic address: sedah1984@163.com., Tao J; Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China. Electronic address: taojinping2020@163.com., Li L; Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China. Electronic address: liliqiang@bjmu.edu.cn., Ding J; Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China. Electronic address: as110_007@163.com., Sheng X; Department of Genitourinary Oncology, Peking University Cancer Hospital & Institute, Beijing, China. Electronic address: doctor_sheng@126.com., Zhu H; Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China. Electronic address: zhuhuabch@pku.edu.cn., Yang Z; Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China. Electronic address: pekyz@163.com.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Sep; Vol. 178, pp. 117151. Date of Electronic Publication: 2024 Jul 18.
DOI: 10.1016/j.biopha.2024.117151
Abstrakt: Background: Trop-2 is closely related to the development and progression of a variety of tumours and poor prognosis. This study aimed to construct an iodine-124 ( 124 I)-labelled antibody-drug conjugate (ADC) positron emission tomography (PET) probe which could noninvasively image Trop-2 in vivo, providing an important method for the diagnosis of tumours with high Trop-2 expression in clinical practice and monitoring their treatment.
Methods: In this study, a novel Trop-2-targeting molecular probe, 124 I-IMMU-132, was constructed to better reveal the expression of Trop-2. The targeting and binding abilities of the probe to Trop-2-positive tumours were investigated in Capan-1/MDA-MB-468/Mcf-7 cells and their animal models.
Results: The constructed 124 I-IMMU-132 probe maintained both reliable radiochemical characteristics and binding affinity (K d = 2.200 nmol/L). The uptake of the probe by Trop-2-positive Capan-1/MDA-MB-468 cells increased in a time-dependent manner. The probe bound specifically to Capan-1/MDA-MB-468 tumours in vivo. The SUVmax Tumour/muscle ratio gradually increased with time, from 4.30 ± 0.55-10.78 ± 1.80 (p < 0.01) in the Capan-1 model and from 8.84 ± 0.95-32.20 ± 2.9 (p < 0.001) in the MDA-MB-468 model. The biodistribution and pharmacokinetics of 124 I-IMMU-132 in a mouse model were consistent with the imaging results, and the dosimetry estimation in humans was acceptable.
Conclusions: 124 I-IMMU-132 PET is a promising imaging technique for delineating Trop-2-positive tumours. It has great potential in early diagnosis and targeted selection of patients that could benefit from its application.
Competing Interests: Declaration of Competing Interest We declare that none of our authors have financial or other conflicts of interest that might be construed as influencing the results or interpretation of our study. This study has not been presented anywhere else.
(Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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