Huang Wenpeng, Wang Tianyao, Chao Fangfang, Yang Qi, Mixdorf Jason C, Li Liming, Engle Jonathan W, Fan Yu, Kang Lei, Cai Weibo
Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China.
Department of Nuclear Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province 450052, China.
Mol Pharm. 2025 Apr 7;22(4):2266-2275. doi: 10.1021/acs.molpharmaceut.5c00069. Epub 2025 Mar 9.
Trop2 exhibits significantly elevated expression in numerous solid malignancies, playing a crucial role in tumor advancement, whereas its presence in healthy tissues is minimal. In this study, we investigated Trop2 expression in bladder cancer models using [Cu]Cu-NOTA-Trodelvy for immunoPET imaging. In HT-1376 models, [Cu]Cu-NOTA-Trodelvy effectively visualized tumor as early as 12 h p.i. (10.30 ± 1.45% ID/g), with tumor uptake increasing and peaking at 48 h p.i. (13.73 ± 1.16% ID/g), highlighting its potential for tumor imaging. Control groups also demonstrated low tumor uptake (5.27 ± 1.14% ID/g at 48 h in the blocking group; 6.33 ± 0.74% ID/g at 48 h in UM-UC-3; 4.50 ± 0.30% ID/g at 48 h in the [Cu]Cu-NOTA-IgG group). Long-term fluorescence imaging further confirmed the tumor uptake rate in the IRDye 800CW-Trodelvy group was significantly higher than in the IRDye 800CW-Trodelvy blockade group ( < 0.001). Our findings demonstrated that [Cu]Cu-NOTA-Trodelvy enables specific and prolonged tumor accumulation in bladder cancer models, providing precise and noninvasive monitoring of Trop2 expression.
Trop2在众多实体恶性肿瘤中表达显著升高，在肿瘤进展中起关键作用，而在健康组织中的表达极少。在本研究中，我们使用[铜]铜- NOTA - Trodelvy进行免疫PET成像，研究了膀胱癌模型中Trop2的表达。在HT - 1376模型中，[铜]铜- NOTA - Trodelvy在注射后12小时即可有效显示肿瘤（10.30±1.45% ID/g），肿瘤摄取量在注射后48小时增加并达到峰值（13.73±1.16% ID/g），突出了其在肿瘤成像方面的潜力。对照组的肿瘤摄取量也较低（阻断组在48小时时为5.27±1.14% ID/g；UM - UC - 3在48小时时为6.33±0.74% ID/g；[铜]铜- NOTA - IgG组在48小时时为4.50±0.30% ID/g）。长期荧光成像进一步证实，IRDye 800CW - Trodelvy组的肿瘤摄取率显著高于IRDye 800CW - Trodelvy阻断组（<0.001）。我们的研究结果表明，[铜]铜- NOTA - Trodelvy能够在膀胱癌模型中实现特异性和长时间的肿瘤蓄积，为Trop2表达提供精确且无创的监测。
