[89Zr]Zr-DFO-Trodelvy immunoPET for noninvasive Trop2 imaging in bladder cancer.

Abstract

Purpose: The Trop2-targeting antibody-drug conjugate (ADC), sacituzumab govitecan (Trodelvy^TM), 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 [⁸⁹Zr]Zr-DFO-Trodelvy.

Materials and methods: Trop2 expression levels in bladder cancer cell lines were measured using flow cytometry and immunofluorescence staining. Radiolabeling of DFO-Trodelvy with ⁸⁹Zr was carried out in Na₂CO₃ buffer at pH 7 (37°C, 1.5 h). ImmunoPET imaging with [⁸⁹Zr]Zr-DFO-Trodelvy was performed at multiple time points to evaluate in vivo targeting. Additionally, tumor tissues from tumor-bearing mice were analyzed by immunofluorescence.

Results: The radiochemical yield of [⁸⁹Zr]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, P = 0.0005). Co-injection with 2 mg of unlabeled Trodelvy significantly reduced tumor uptake in HT1376 models (4.50 ± 0.51 %ID/g, P = 0.0004), confirming target specificity. At 48 h, a high tumor-to-background ratio was observed, indicating selective accumulation in tumor tissue.

Conclusions: [⁸⁹Zr]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.