Background Considering trophoblast cell surface antigen 2 (Trop2) is overexpressed in a wide range of human epithelial cancers, it presents an attractive target for the 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 values 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 SUVmax) 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). When 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 non-invasive method for comprehensively assessing Trop2 expression in tumors, which can improve the diagnosis and staging for cancer patients, and aid in the decision-making for Trop2-targeted therapies and advancing personalized treatment.

中文翻译：

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68Ga-MY6349 PET/CT 成像评估 Trop2 在多种类型癌症中的表达。


背景 考虑到滋养层细胞表面抗原 2 （Trop2） 在广泛的人类上皮癌中过表达，它为多种癌症的诊断和治疗提供了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，并提出了一项前瞻性、研究者发起的试验，以探索 68Ga-MY6349 PET/CT 的临床价值。方法 在这项转化研究中，前瞻性招募了 90 名接受 68Ga-MY6349 PET/CT 的 15 种癌症患者。其中，78 例患者接受了配对 68Ga-MY6349 和 18F-FDG PET/CT，12 例前列腺癌患者接受了配对 68Ga-MY6349 和 68Ga-PSMA-11 PET/CT。结果 在 15 种癌症的 90 例患者中，68Ga-MY6349 在肿瘤中的摄取普遍较高，但存在异质性，因病灶、患者和癌症类型而异。免疫组化测定的 Trop2 表达水平与原发性和转移性肿瘤部位的 68Ga-MY6349 摄取高度相关。68Ga-MY6349 PET/CT 显示在某些类型的癌症中，肿瘤摄取 （通过 SUVmax 量化） 高于 18F-FDG PET/CT，包括乳腺癌 （7.2 vs. 5.4，P < 0.001）、前列腺癌 （9.2 vs. 3.0，P < 0.001） 和甲状腺癌 （8.5 vs. 3.7，P < 0.001）。与 68Ga-PSMA-11 相比，68Ga-MY6349 PET/CT 表现出相当的病灶摄取 （12.2 vs. 12.5，P = 0.223），但肿瘤背景对比更好 （15.8 vs. 12.2，P < 0.001） 原发性和转移性前列腺癌，允许可视化更多的转移病灶。 结论 68Ga-MY6349 PET/CT 是一种综合评估 Trop2 在肿瘤中表达的无创方法，可改善癌症患者的诊断和分期，有助于 Trop2 靶向治疗的决策和推进个体化治疗。