⁶⁸Ga-MY6349 PET/CT imaging to assess Trop2 expression in multiple types of cancer

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Abstract

BACKGROUND Considering that trophoblast cell-surface antigen 2 (Trop2) is overexpressed in a wide range of human epithelial cancers, it presents an attractive target for diagnosis and treatment of multiple types of cancer. Herein, we have developed a Trop2-specific radiotracer, 68Ga-MY6349, and present a prospective, investigator-initiated trial to explore the clinical value of 68Ga-MY6349 PET/CT.METHODS In this translational study, 90 patients with 15 types of cancer who underwent 68Ga-MY6349 PET/CT were enrolled prospectively. Among them, 78 patients underwent paired 68Ga-MY6349 and 18F-FDG PET/CT, and 12 patients with prostate cancer underwent paired 68Ga-MY6349 and 68Ga-PSMA-11 PET/CT.RESULTS Among the 90 patients across 15 types of cancer, 68Ga-MY6349 uptake in tumors was generally high but heterogeneous, varying among lesions, patients, and cancer types. Trop2 expression level determined by immunohistochemistry was highly correlated with 68Ga-MY6349 uptake at primary and metastatic tumor sites. 68Ga-MY6349 PET/CT showed higher tumor uptake (quantified by maximum standardized uptake value) than 18F-FDG PET/CT in certain types of cancer, including breast (7.2 vs. 5.4, P < 0.001), prostate (9.2 vs. 3.0, P < 0.001), and thyroid cancers (8.5 vs. 3.7, P < 0.001). Compared with 68Ga-PSMA-11, 68Ga-MY6349 PET/CT exhibited comparable lesion uptake (12.2 vs. 12.5, P = 0.223) but a better tumor-to-background contrast (15.8 vs. 12.2, P < 0.001) for primary and metastatic prostate cancer, allowing visualization of more metastatic lesions.CONCLUSION 68Ga-MY6349 PET/CT is a noninvasive method for comprehensively assessing Trop2 expression in tumors, which can improve diagnosis and staging for cancer patients and aid in decision making for Trop2-targeted therapies and advancing of personalized treatment.TRIAL REGISTRATION ClinicalTrials.gov NCT06188468.FUNDING National Natural Science Foundation of China, National Key R&D Program of China, Nuclear Energy R&D project, Fujian Research and Training Grants for Young and Middle-aged Leaders in Healthcare, Key Scientific Research Program for Young Scholars in Fujian, and Fujian Natural Science Foundation for Distinguished Young Scholars.

Authors

Haojun Chen, Liang Zhao, Yizhen Pang, Jiyun Shi, Hannan Gao, Yining Sun, Jianhao Chen, Hao Fu, Jiayu Cai, Lingyu Yu, Ru Zeng, Long Sun, Hua Wu, Zhanxiang Wang, Fan Wang