Xue Xinyu, Liao Wenfang, Guo Xiaotian, Chen Fei, Zhu Bao
Department of Nuclear Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu 214023, P. R. China.
Anal Chem. 2025 Jun 24;97(24):12803-12812. doi: 10.1021/acs.analchem.5c01857. Epub 2025 Jun 9.
High reactive oxygen species (ROS) serve as important signaling molecules in the tumor microenvironment, and their excessive generation is closely associated with tumor growth, drug resistance, and metastasis of tumors. Rrecently, probes based on 1,3-cyclohexanedione have been proposed, enabling real-time monitoring of ROS levels in the tumor microenvironment. Herein, as a proof of concept, we aimed at synthesizing a novel tumor diagnostic probe, Ga-NOTA-cRGD, by connecting NOTA and the tumor-targeting peptide cRGD with a 1,3-cyclohexanedione group that specifically undergoes cross-linking with sulfenic acid, to enhance the targeting and prolong the imaging time of the probe in tumors. Moreover, the study also evaluated the capability of the synthesized probe in both and experiments. The results indicated that the radiolabeling process was efficient and stable, and the stability of the probe under physiological conditions was also outstanding. Compared to the control probe Ga-NOTA-cRGD-1 lacking 1,3-cyclohexanedione, the experimental probe Ga-NOTA-cRGD-2 not only exhibited significant improvements in cell uptake efficiency, tumor imaging contrast, and biodistribution characteristics but also demonstrated enhanced cell affinity and a prolonged biological half-life. The addition of 1,3-cyclohexanedione enhanced the probe's tumor-targeting capability, resulting in higher uptake in A549 tumor cells. In conclusion, this study confirmed the crucial role of 1,3-cyclohexanedione in prolonging tumor targeting. It is anticipated to provide a theoretical foundation and experimental support for the development of more efficient probes in the future.
高活性氧（ROS）是肿瘤微环境中的重要信号分子，其过量产生与肿瘤生长、耐药性及肿瘤转移密切相关。最近，基于1,3 - 环己二酮的探针被提出，可实现对肿瘤微环境中ROS水平的实时监测。在此，作为概念验证，我们旨在合成一种新型肿瘤诊断探针Ga - NOTA - cRGD，通过将NOTA和肿瘤靶向肽cRGD与一个能与亚磺酸特异性交联的1,3 - 环己二酮基团相连，以增强探针在肿瘤中的靶向性并延长其成像时间。此外，该研究还在体外和体内实验中评估了合成探针的性能。结果表明，放射性标记过程高效且稳定，探针在生理条件下的稳定性也很出色。与缺乏1,3 - 环己二酮的对照探针Ga - NOTA - cRGD - 1相比，实验探针Ga - NOTA - cRGD - 2不仅在细胞摄取效率、肿瘤成像对比度和生物分布特性方面有显著改善，还表现出增强的细胞亲和力和延长的体内生物半衰期。1,3 - 环己二酮的加入增强了探针的肿瘤靶向能力，导致其在A549肿瘤细胞中的摄取更高。总之，本研究证实了1,3 - 环己二酮在延长肿瘤靶向方面的关键作用。预计为未来开发更高效的探针提供理论基础和实验支持。
