Intraoperative surgical margin assessment remains a challenge during breast-conserving surgery. Here, we report a combined strategy of immuno–positron emission tomography (PET) for preoperative detection of breast cancer and guided assessment of margins in breast-conserving surgery through second near-infrared (NIR-II) fluorescence imaging of trophoblastic cell surface antigen 2 (TROP2). We demonstrated that the intensity of PET signals in the tumors was nearly five times higher than in normal breast tissue with a zirconium-89 tracer conjugated to sacituzumab govitecan (SG) in a mouse spontaneous breast cancer model, enabling the identification of tumors. We further generated a NIR-II probe of indocyanine green conjugated to SG (ICG-SG) and developed a rapid incubation imaging method for intraoperative margin assessment in a relevant time window for the operation workflow. The ICG-SG NIR-II fluorescence image guidance was first verified to remove tumors completely and accurately in mouse breast cancer models. Moreover, the rapid incubation imaging method was applied to distinguish benign and malignant breast lesions in samples from 26 patients with breast cancer. Therefore, we have developed both nuclide and optical probes targeting TROP2 for rapid and precise identification of tumor margins during breast-conserving surgery in humans.

中文翻译：

---

使用 TROP2 近红外成像探头进行肿瘤切缘的术中评估，以实现人类保乳手术


在保乳手术中，术中手术切缘评估仍然是一个挑战。在这里，我们报告了一种免疫-正电子发射断层扫描 （PET） 的联合策略，用于术前检测乳腺癌，并通过滋养细胞表面抗原 2 （TROP2） 的第二次近红外 （NIR-II） 荧光成像指导保乳手术中的切缘评估。在小鼠自发性乳腺癌模型中，我们证明肿瘤中 PET 信号的强度比正常乳腺组织中高出近五倍，其中锆 89 示踪剂与 sacituzumab govitecan （SG） 偶联，能够识别肿瘤。我们进一步生成了吲哚菁绿与 SG （ICG-SG） 的 NIR-II 探针，并开发了一种快速孵育成像方法，用于在手术工作流程的相关时间窗口内进行术中切缘评估。首次验证了 ICG-SG NIR-II 荧光图像引导在小鼠乳腺癌模型中完全准确地去除肿瘤。此外，应用快速孵育成像方法区分 26 例乳腺癌患者样本中的良恶性乳腺病变。因此，我们开发了靶向 TROP2 的核素和光学探针，用于在人类保乳手术中快速、精确地识别肿瘤边缘。