由于缺乏可识别的分子靶点，三阴性乳腺癌（TNBC）的诊断和治疗面临巨大挑战。 Nectin4在包括TNBC在内的多种肿瘤中高表达，与肿瘤的发生、侵袭、进展和不良预后相关。因此，Nectin4是一种新兴的用于诊断和治疗TNBC的生物标志物。非侵入性量化 Nectin4 表达水平的 PET 成像方法可能有助于 TNBC 的诊断和分类。在本研究中，使用一种新型双环肽分子探针[68Ga]Ga-DN68来评估Nectin4在肿瘤中的表达。 [68Ga]Ga-DN68 的放射性标记率超过 97%，同时保持超过 99% 的放射化学纯度。体外实验表明，[68Ga]Ga-DN68能够有效靶向肿瘤细胞中的Nectin4，并且MC38-Nectin4细胞（Nectin4 ）的细胞摄取显着高于MC38细胞（Nectin4-）。生物分布和PET成像研究一致表明，[68Ga]Ga-DN68在MC38-Nectin4和MDA-MB-468肿瘤中特异性积累，且明显高于MC38。当与冷 DN68 共同注射时，特异性积累可以阻断肿瘤对 MDA-MB-468 的摄取。值得注意的是，肿瘤部位的信噪比随着时间的推移逐渐增加，在 1 小时时达到峰值。这些结果强烈表明，[68Ga]Ga-DN68 作为 TNBC 成像中的 PET 示踪剂具有广阔的应用前景。版权所有 © 2024 Elsevier Inc. 保留所有权利。

The diagnosis and treatment of triple negative breast cancer (TNBC) are huge challenges due to the lack of identifiable molecular targets. The high expression of Nectin4 in a variety of tumors, including TNBC, is associated with the occurrence, invasion, progression and poor prognosis of tumors. Therefore, Nectin4 is an emerging biomarker for the diagnosis and treatment of TNBC. A PET imaging method to non-invasively quantify Nectin4 expression levels may aid in TNBC diagnosis and classification. In this study, a novel bicyclic peptide molecular probe [68Ga]Ga-DN68 was used to evaluate the expression of Nectin4 in tumors. The radiolabeling rate of [68Ga]Ga-DN68 was over 97 %, while maintaining more than 99 % radiochemical purity. In vitro experiments showed that [68Ga]Ga-DN68 could effectively target Nectin4 in tumor cells, and the cellular uptake of MC38-Nectin4 cells (Nectin4+) was significantly higher than that of MC38 cells (Nectin4-). Biodistribution and PET imaging studies consistently showed that [68Ga]Ga-DN68 was specifically accumulated in MC38-Nectin4 and MDA-MB-468 tumors, which was significantly higher than that of MC38. When co-injected with cold DN68, the specific accumulation could block the tumor uptake of MDA-MB-468. Notably, the signal-to-noise ratio at the tumor site gradually increased over time, reaching a peak at 1 h. These results strongly suggest that [68Ga]Ga-DN68 has broad application prospects as a PET tracer in TNBC imaging.Copyright © 2024 Elsevier Inc. All rights reserved.