Chen Haojun, Zhao Liang, Pang Yizhen, Shi Jiyun, Gao Hannan, Sun Yining, Chen Jianhao, Fu Hao, Cai Jiayu, Yu Lingyu, Zeng Ru, Sun Long, Wu Hua, Wang Zhanxiang, Wang Fan
Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials, Xiamen Institute of Rare Earth Materials, Haixi Institute, Chinese Academy of Sciences, Xiamen, China.
J Clin Invest. 2024 Nov 7;135(1):e185408. doi: 10.1172/JCI185408.
BACKGROUNDConsidering 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.METHODSIn 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.RESULTSAmong 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.CONCLUSION68Ga-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 REGISTRATIONClinicalTrials.gov NCT06188468.FUNDINGNational 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.
背景
鉴于滋养层细胞表面抗原2（Trop2）在多种人类上皮癌中过度表达，它是多种癌症诊断和治疗的一个有吸引力的靶点。在此，我们开发了一种Trop2特异性放射性示踪剂68Ga-MY6349，并开展了一项由研究者发起的前瞻性试验，以探索68Ga-MY6349 PET/CT的临床价值。
方法
在这项转化研究中，前瞻性纳入了90例患有15种癌症并接受68Ga-MY6349 PET/CT检查的患者。其中，78例患者接受了68Ga-MY6349和18F-FDG PET/CT的配对检查，12例前列腺癌患者接受了68Ga-MY6349和68Ga-PSMA-11 PET/CT的配对检查。
结果
在这90例患有15种癌症的患者中，肿瘤对68Ga-MY6349的摄取总体较高但存在异质性，在病变、患者和癌症类型之间有所不同。免疫组织化学测定的Trop2表达水平与原发和转移肿瘤部位的68Ga-MY6349摄取高度相关。在某些类型的癌症中，包括乳腺癌（7.2对5.4，P<0.001）、前列腺癌（9.2对3.0，P<0.001）和甲状腺癌（8.5对3.7，P<0.001），68Ga-MY6349 PET/CT显示出比18F-FDG PET/CT更高的肿瘤摄取（通过最大标准化摄取值量化）。与68Ga-PSMA-11相比，68Ga-MY6349 PET/CT对原发和转移前列腺癌的病变摄取相当（12.2对12.5，P = 0.22），但肿瘤与背景的对比度更好（15.8对12.2，P<0.001），能够显示更多的转移病灶。
结论
68Ga-MY6349 PET/CT是一种全面评估肿瘤中Trop2表达的非侵入性方法，可改善癌症患者的诊断和分期，并有助于Trop2靶向治疗的决策制定和个性化治疗的推进。
试验注册
ClinicalTrials.gov NCT06188468。
资助
中国国家自然科学基金、中国国家重点研发计划、核能研发项目、福建省医疗卫生中青年领军人才培养项目、福建省青年科技人才重点科研项目、福建省杰出青年科学基金。
