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实体瘤中靶向Trop2的分子成像:当前进展与未来展望

Trop2-Targeted Molecular Imaging in Solid Tumors: Current Advances and Future Outlook.

作者信息

Liu Yongshun, Huang Wenpeng, Saladin Rachel J, Hsu Jessica C, Cai Weibo, Kang Lei

机构信息

Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China.

Departments of Radiology and Medical Physics, University of Wisconsin─Madison, Madison, Wisconsin 53705, United States.

出版信息

Mol Pharm. 2024 Dec 2;21(12):5909-5928. doi: 10.1021/acs.molpharmaceut.4c00848. Epub 2024 Nov 13.

Abstract

Trophoblast cell surface antigen 2 (Trop2), a transmembrane glycoprotein, plays a dual role in physiological and pathological processes. In healthy tissues, Trop2 facilitates development and orchestrates intracellular calcium signaling. However, its overexpression in numerous solid tumors shifts its function toward driving cell proliferation and metastasis, thus leading to a poor prognosis. The clinical relevance of Trop2 is underscored by its utility as both a biomarker for diagnostic imaging and a target for therapy. Notably, the U.S. Food and Drug Administration (FDA) has approved sacituzumab govitecan (SG), a novel Trop2-targeted agent, for treating triple-negative breast cancer (TNBC) and refractory urothelial cancer, highlighting the significance of Trop2 in clinical oncology. Molecular imaging, a powerful tool for visualizing and quantifying biological phenomena at the molecular and cellular levels, has emerged as a critical technique for studying Trop2. This approach encompasses various modalities, including optical imaging, positron emission tomography (PET), single photon emission computed tomography (SPECT), and targeted antibodies labeled with radioactive isotopes. Incorporating Trop2-targeted molecular imaging into clinical practice is vital for the early detection, prognostic assessment, and treatment planning of a broad spectrum of solid tumors. Our review captures the latest progress in Trop2-targeted molecular imaging, focusing on both diagnostic and therapeutic applications across diverse tumor types, including lung, breast, gastric, pancreatic, prostate, and cervical cancers, as well as salivary gland carcinomas. We critically evaluate the current state by examining the relevant applications, diagnostic accuracy, therapeutic efficacy, and inherent limitations. Finally, we analyze the challenges impeding widespread clinical application and offer insights into strategies for advancing the field, thereby guiding future research endeavors.

摘要

滋养层细胞表面抗原2(Trop2)是一种跨膜糖蛋白,在生理和病理过程中发挥双重作用。在健康组织中,Trop2促进发育并协调细胞内钙信号传导。然而,它在许多实体瘤中的过度表达使其功能转向驱动细胞增殖和转移,从而导致预后不良。Trop2作为诊断成像的生物标志物和治疗靶点的实用性凸显了其临床相关性。值得注意的是,美国食品药品监督管理局(FDA)已批准新型Trop2靶向药物戈沙妥珠单抗(SG)用于治疗三阴性乳腺癌(TNBC)和难治性尿路上皮癌,这突出了Trop2在临床肿瘤学中的重要性。分子成像作为一种在分子和细胞水平可视化和量化生物现象的强大工具,已成为研究Trop2的关键技术。这种方法包括多种模式,包括光学成像、正电子发射断层扫描(PET)、单光子发射计算机断层扫描(SPECT)以及用放射性同位素标记的靶向抗体。将Trop2靶向分子成像纳入临床实践对于多种实体瘤的早期检测、预后评估和治疗规划至关重要。我们的综述总结了Trop2靶向分子成像的最新进展,重点关注包括肺癌、乳腺癌、胃癌、胰腺癌、前列腺癌和宫颈癌以及唾液腺癌在内的多种肿瘤类型的诊断和治疗应用。我们通过检查相关应用、诊断准确性、治疗效果和固有局限性来批判性地评估当前状态。最后,我们分析了阻碍广泛临床应用的挑战,并提供了推进该领域的策略见解,从而指导未来的研究工作。

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