Institute of Molecular Medicine, College of Life and Health Sciences, Northeastern University, Shenyang 110167, China.
State Key Laboratory of Drug Research, Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
J Med Chem. 2023 Jun 8;66(11):7523-7533. doi: 10.1021/acs.jmedchem.3c00347. Epub 2023 May 29.
Human epidermal growth factor receptor 2 (HER2) may serve as a valid target for diagnosis of cancer. The probes with capability for near-infrared window one region II (NIR-II) and positron emission tomography (PET) dual-modal imaging are highly desired for HER2-positive tumor detection. Herein, three HER2-targeted peptides were designed and further modified with indocyanine green (ICG) and 2,2',2″,2″-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA), which were used for NIR-II imaging and complexation with Ga for PET. Among the resulted probes (DOTA-ZC01-ICG, DOTA-KSP-ICG, and DOTA-ZC02-ICG), NIR-II imaging revealed that DOTA-ZC02-ICG had the best tumor imaging performance in SKOV3 tumor-bearing mice. The highest T/N ratio (5.4) was achieved at 4 h post-injection. Furthermore, DOTA-ZC02-ICG was radiolabeled with Ga to generate [Ga]-DOTA-ZC02-ICG for PET, and it clearly delineated at 0.5, 1, and 2 h post-injection. The tumor uptake reached 1.9 %ID/g at 0.5 h, and the tumor uptakes were significantly inhibited in the blocking study ( < 0.05). Overall, it provides a promising technique for tumor dual-modal imaging and a new molecular scaffold for developing HER2-targeted theranostic agents.
人表皮生长因子受体 2（HER2）可作为癌症诊断的有效靶点。具有近红外窗口一区 II（NIR-II）和正电子发射断层扫描（PET）双模式成像能力的探针非常适合用于 HER2 阳性肿瘤的检测。在此，设计了三种 HER2 靶向肽，并进一步用吲哚菁绿（ICG）和 2,2',2″,2″-(1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸（DOTA）进行修饰，用于 NIR-II 成像和与 Ga 的络合用于 PET。在所得到的探针（DOTA-ZC01-ICG、DOTA-KSP-ICG 和 DOTA-ZC02-ICG）中，NIR-II 成像显示 DOTA-ZC02-ICG 在 SKOV3 荷瘤小鼠中具有最佳的肿瘤成像性能。在注射后 4 小时达到最高的 T/N 比（5.4）。此外，用 Ga 对 DOTA-ZC02-ICG 进行放射性标记，生成 [Ga]-DOTA-ZC02-ICG 用于 PET，在注射后 0.5、1 和 2 小时可清晰显示。肿瘤摄取率在 0.5 小时达到 1.9%ID/g，在阻断研究中肿瘤摄取显著抑制（<0.05）。总的来说，它为肿瘤双模式成像提供了一种有前途的技术，为开发 HER2 靶向治疗剂提供了一种新的分子支架。
