不充分的细胞减灭术（CRS）已被确定为腹膜转移病例患者预后不良的一个预后因素。虽然成像探针用于识别腹膜转移以促进 CRS，但许多探针表现出高背景信号，由于清除时间延长，导致显着延迟实现令人满意的肿瘤与正常比率 (TNR)。在本研究中，我们设计了一种名为 Tras-AA-Cy NH2 的新型荧光探针，它能够相对快速地对皮下肿瘤和腹膜肿瘤进行成像，同时保持较高的 TNR。从机制上讲，Tras-AA-Cy NH2 表现出选择性靶向癌细胞表面的人表皮生长因子受体 2。内化后，它会经历过度表达的组织蛋白酶催化的酶裂解，导致随后释放近红外荧光团。因此，Tras-AA-Cy NH2 在皮下肿瘤小鼠中，6 小时时的 TNR 为 7.8，24 小时时的 TNR 为 21.4。即使在体内循环 522 小时后，TNR 仍保持在 5 以上，表明超长的成像时间窗口。值得注意的是，Tras-AA-Cy NH2已成功用于腹膜肿瘤特异性成像，并进一步证实了其利用人体切除组织进行肿瘤组织特异性识别的能力。总之，这些发现强调了 Tras-AA-Cy NH2 用于腹膜肿瘤可视化的合理设计。版权所有 © 2023 Elsevier Masson SAS。版权所有。

Inadequate cytoreductive surgery (CRS) has been identified as a prognostic factor for poor patient outcomes in cases of peritoneal metastasis. While imaging probes are used to identify peritoneal metastasis to facilitate CRS, many of these probes exhibit high background signals, resulting in a significant delay in achieving a satisfactory tumor-to-normal ratio (TNR) due to prolonged clearance time. In this study, we designed a novel fluorescent probe named Tras-AA-Cy NH2, which enables the relatively rapid imaging of subcutaneous tumors and peritoneal tumors while maintaining a high TNR. Mechanistically, Tras-AA-Cy NH2 exhibits selective targeting towards the Human epidermal growth factor receptor 2 on the surface of cancer cells. Following internalization, it undergoes enzymatic cleavage catalyzed by the overexpressed cathepsin, leading to the subsequent release of near-infrared fluorophores. Consequently, Tras-AA-Cy NH2 achieved a TNR of 7.8 at 6 h and 21.4 at 24 h in subcutaneous tumor mice. Even after 522 h of in vivo circulation, the TNR remained above 5, indicating an ultralong imaging time window. It is noteworthy that Tras-AA-Cy NH2 has demonstrated successful utilization for peritoneal tumor-specific imaging and further affirmed its tumor tissue-specific recognition capability using human resected tissues. In summary, these findings underscore the rational design of Tras-AA-Cy NH2 for visualizing peritoneal tumors.Copyright © 2023 Elsevier Masson SAS. All rights reserved.