Huang Wenpeng, Sun Xinyao, Liang Yutong, Mixdorf Jason C, Yang Qi, Engle Jonathan W, Xiao Xiaoyan, Li Liming, Kang Lei, Cai Weibo
Department of Nuclear Medicine, Peking University First Hospital Beijing 100034, China.
Departments of Radiology and Medical Physics, University of Wisconsin - Madison Madison, WI 53705, USA.
Am J Nucl Med Mol Imaging. 2025 Jun 25;15(3):87-96. doi: 10.62347/KKEE6954. eCollection 2025.
The Trop2-targeting antibody-drug conjugate (ADC), sacituzumab govitecan (Trodelvy), demonstrates significant therapeutic efficacy in targeting Trop2-expressing tumors. In this study, we utilized immunoPET imaging to assess Trop2 expression in bladder cancer models using [Zr]Zr-DFO-Trodelvy.
Trop2 expression levels in bladder cancer cell lines were measured using flow cytometry and immunofluorescence staining. Radiolabeling of DFO-Trodelvy with Zr was carried out in NaCO buffer at pH 7 (37°C, 1.5 h). ImmunoPET imaging with [Zr]Zr-DFO-Trodelvy was performed at multiple time points to evaluate targeting. Additionally, tumor tissues from tumor-bearing mice were analyzed by immunofluorescence.
The radiochemical yield of [Zr]Zr-DFO-Trodelvy was >90%, with radiochemical purity exceeding 99%. Trop2 expression was high in HT1376 cells and low in T24 cells. ImmunoPET imaging demonstrated effective visualization of tumors in HT1376 models as early as 6 h post-injection, with tumor uptake reaching peak at 48 h (16.33 ± 0.90 %ID/g), followed by a gradual decline. In contrast, T24 tumors showed significantly lower uptake (6.20 ± 0.99 %ID/g, = 0.0005). Co-injection with 2 mg of unlabeled Trodelvy significantly reduced tumor uptake in HT1376 models (4.50 ± 0.51 %ID/g, = 0.0004), confirming target specificity. At 48 h, a high tumor-to-background ratio was observed, indicating selective accumulation in tumor tissue.
[Zr]Zr-DFO-Trodelvy enables precise immunoPET imaging of bladder cancer models with high Trop2 expression, demonstrating specific and sustained tumor accumulation. These findings highlight the potential of this imaging approach for the noninvasive assessment of Trop2 expression.
靶向Trop2的抗体药物偶联物（ADC），即戈沙妥珠单抗（Trodelvy），在靶向表达Trop2的肿瘤方面显示出显著的治疗效果。在本研究中，我们利用免疫正电子发射断层显像（immunoPET）成像，使用[锆]Zr-DFO-Trodelvy评估膀胱癌模型中的Trop2表达。
使用流式细胞术和免疫荧光染色测量膀胱癌细胞系中的Trop2表达水平。在pH值为7的NaCO缓冲液中（37°C，1.5小时）用Zr对DFO-Trodelvy进行放射性标记。在多个时间点进行[锆]Zr-DFO-Trodelvy免疫正电子发射断层显像，以评估靶向性。此外，通过免疫荧光分析荷瘤小鼠的肿瘤组织。
[锆]Zr-DFO-Trodelvy的放射化学产率>90%，放射化学纯度超过99%。HT1376细胞中Trop2表达高，T24细胞中Trop2表达低。免疫正电子发射断层显像显示，早在注射后6小时就能有效观察到HT1376模型中的肿瘤，肿瘤摄取在48小时达到峰值（16.33±0.90%ID/g），随后逐渐下降。相比之下，T24肿瘤的摄取明显较低（6.20±0.99%ID/g，P = 0.0005）。在HT1376模型中共同注射2毫克未标记的Trodelvy可显著降低肿瘤摄取（4.50±0.51%ID/g，P = 0.0004），证实了靶点特异性。在48小时时，观察到高肿瘤与背景比值，表明在肿瘤组织中选择性积聚。
[锆]Zr-DFO-Trodelvy能够对高表达Trop2的膀胱癌模型进行精确的免疫正电子发射断层显像，显示出特异性和持续性的肿瘤积聚。这些发现突出了这种成像方法在无创评估Trop2表达方面的潜力。
