[ 99m Tc]Tc-MY6349 Probe for Trop2-Targeted SPECT Imaging: From Preclinical to Pilot Clinical Study

作者：Yining Sun, Zhixin Hao, Hannan Gao, Guangjie Yang, Bo Pan, Zhu Min, Yakun Wan, Jiyun Shi, Li Huo, Haojun Chen, Fan Wang · 发表于：Journal of Nuclear Medicine · 年份：2025 · DOI：10.2967/jnumed.124.268564 · 被引用次数：17 · 研究领域：HER2/EGFR in Cancer Research、Radiopharmaceutical Chemistry and Applications、Monoclonal and Polyclonal Antibodies Research

The trophoblast cell-surface antigen 2 (Trop2) is markedly overexpressed in breast cancers, with a particularly high incidence in triple-negative breast cancer. The therapeutic relevance of Trop2 expression is underscored by the approval of an antibody–drug conjugate for triple-negative breast cancer treatment. However, there is no a predictive technique for accurate whole-body mapping of Trop2 expression in patients. In this study, we developed a novel Trop2-specific molecular probe, [ 99m Tc]Tc-MY6349, and evaluated its safety and feasibility for detecting Trop2 expression in breast cancer using SPECT/CT imaging. Methods: Trop2 expression in different breast cancer cell lines was assessed via immunofluorescence and flow cytometry. The Trop2-specific nanobody MY6349 was site-specifically labeled with 99m Tc via a C-terminal GGGC tag, and its binding affinity to the Trop2 receptor was tested in vitro. The in vivo tumor uptake and distribution of [ 99m Tc]Tc-MY6349 were examined through SPECT imaging and biodistribution studies. Furthermore, a pilot clinical study of [ 99m Tc]Tc-MY6349 SPECT/CT was conducted in 8 patients with breast cancer, and the results were compared with [ 18 F]FDG PET/CT. Results: [ 99m Tc]Tc-MY6349 achieved a greater than 95% radiochemical purity after purification. In vitro and in vivo experiments demonstrated the binding specificity of [ 99m Tc]Tc-MY6349 to the Trop2 receptor. In vivo imaging and biodistribution studies revealed a ...