利用 TROP2 近红外成像探针对肿瘤边缘进行术中评估，以实现人类保乳手术

IF 15.8 1区医学 Q1 CELL BIOLOGY

Science Translational Medicine Pub Date : 2024-10-16 DOI:10.1126/scitranslmed.ado2461

Weiling Chen, Yongqu Zhang, Lixin Zhang, Xiangjie Luo, Xia Yang, Yuanyuan Zhu, Guimei Wang, Wenhe Huang, Deliang Zhang, Yunzhu Zeng, Ronghui Li, Cuiping Guo, Jiazheng Wang, Zhao Wu, Na Liu, Guojun Zhang

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引用次数: 0

摘要

在保乳手术中，术中手术边缘评估仍是一项挑战。在此，我们报告了一种免疫正电子发射断层扫描（PET）联合策略，通过滋养层细胞表面抗原 2（TROP2）的二次近红外（NIR-II）荧光成像，在保乳手术中进行乳腺癌术前检测和边缘引导评估。我们在小鼠自发性乳腺癌模型中用锆-89示踪剂与沙西珠单抗-戈维替康（SG）共轭，证明肿瘤中的 PET 信号强度是正常乳腺组织的近五倍，从而实现了对肿瘤的识别。我们进一步生成了与 SG 共轭的吲哚菁绿近红外-II 探针（ICG-SG），并开发了一种快速孵育成像方法，用于在手术工作流程的相关时间窗内进行术中边缘评估。ICG-SG近红外-II荧光图像引导技术首次在小鼠乳腺癌模型中得到验证，可完整、准确地切除肿瘤。此外，我们还应用快速孵育成像方法区分了 26 例乳腺癌患者样本中的良性和恶性乳腺病变。因此，我们开发了靶向 TROP2 的核素探针和光学探针，用于在人类保乳手术中快速、精确地识别肿瘤边缘。

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Intraoperative evaluation of tumor margins using a TROP2 near-infrared imaging probe to enable human breast-conserving surgery

Intraoperative surgical margin assessment remains a challenge during breast-conserving surgery. Here, we report a combined strategy of immuno–positron emission tomography (PET) for preoperative detection of breast cancer and guided assessment of margins in breast-conserving surgery through second near-infrared (NIR-II) fluorescence imaging of trophoblastic cell surface antigen 2 (TROP2). We demonstrated that the intensity of PET signals in the tumors was nearly five times higher than in normal breast tissue with a zirconium-89 tracer conjugated to sacituzumab govitecan (SG) in a mouse spontaneous breast cancer model, enabling the identification of tumors. We further generated a NIR-II probe of indocyanine green conjugated to SG (ICG-SG) and developed a rapid incubation imaging method for intraoperative margin assessment in a relevant time window for the operation workflow. The ICG-SG NIR-II fluorescence image guidance was first verified to remove tumors completely and accurately in mouse breast cancer models. Moreover, the rapid incubation imaging method was applied to distinguish benign and malignant breast lesions in samples from 26 patients with breast cancer. Therefore, we have developed both nuclide and optical probes targeting TROP2 for rapid and precise identification of tumor margins during breast-conserving surgery in humans.

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来源期刊

Science Translational Medicine CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL

CiteScore

26.70

自引率

1.20%

发文量

309

审稿时长

1.7 months

期刊介绍： Science Translational Medicine is an online journal that focuses on publishing research at the intersection of science, engineering, and medicine. The goal of the journal is to promote human health by providing a platform for researchers from various disciplines to communicate their latest advancements in biomedical, translational, and clinical research. The journal aims to address the slow translation of scientific knowledge into effective treatments and health measures. It publishes articles that fill the knowledge gaps between preclinical research and medical applications, with a focus on accelerating the translation of knowledge into new ways of preventing, diagnosing, and treating human diseases. The scope of Science Translational Medicine includes various areas such as cardiovascular disease, immunology/vaccines, metabolism/diabetes/obesity, neuroscience/neurology/psychiatry, cancer, infectious diseases, policy, behavior, bioengineering, chemical genomics/drug discovery, imaging, applied physical sciences, medical nanotechnology, drug delivery, biomarkers, gene therapy/regenerative medicine, toxicology and pharmacokinetics, data mining, cell culture, animal and human studies, medical informatics, and other interdisciplinary approaches to medicine. The target audience of the journal includes researchers and management in academia, government, and the biotechnology and pharmaceutical industries. It is also relevant to physician scientists, regulators, policy makers, investors, business developers, and funding agencies.