[68Ga]Ga-NOTA-T4 PET/CT imaging of TROP2 expression in patients with HER2-negative breast cancer.

PURPOSE: Gallium-68([68Ga])-labeled Ga-NOTA-T4 PET/CT is a promising noninvasive imaging tool for visualizing trophoblast cell-surface antigen 2 (TROP2) expression, which could aid clinical decisions regarding TROP2-targeted therapies. This study aims to evaluate the diagnostic performance of [68Ga]Ga-NOTA-T4 PET/CT, a novel TROP2-targeting tracer, for detecting TROP2 expression in HER2-negative breast cancer. METHODS: From September 2023 to March 2025, we retrospectively reviewed patients with HER2-negative breast cancer at Huashan Hospital, Fudan University. All participants underwent [68Ga]Ga-NOTA-T4 PET/CT, with or without [18F]FDG PET/CT. RESULTS: A total of 42 patients were enrolled in the study, among whom 27 underwent both [68Ga]Ga-NOTA-T4 and [18F]FDG PET/CT imaging. [68Ga]Ga-NOTA-T4 PET/CT demonstrated comparable capability to [18F]FDG in identifying both patients and metastatic lesions. Among patients with Luminal B HER2-negative breast cancer, those who had received endocrine therapy or chemotherapy demonstrated significantly higher [⁶⁸Ga]Ga-NOTA-T4 uptake compared to untreated patients (SUVmax: 5.20 ± 5.07 vs. 3.36 ± 3.52; p = 0.008). A similar trend was observed in Luminal A patients, with higher SUVmax values in the treated group; however, the difference did not reach statistical significance (SUVmax: 8.35 ± 6.41 vs. 5.60 ± 4.55; p = 0.241). In TNBC patients, treatment was associated with significantly lower [⁶⁸Ga]Ga-NOTA-T4 uptake compared to those who were untreated (SUVmax: 3.02 ± 2.35 vs. 7.63 ± 5.64; p = 0.008). CONCLUSIONS: [68Ga]Ga-NOTA-T4 PET/CT is a promising tool for visualizing TROP2 expression in breast cancer, with potential applications for patient stratification and precision therapy. In Luminal B breast cancer, SUVmax increased with initial TROP2-targeted ADC therapy but decreased after multiple endocrine therapy or chemotherapy treatments. In TNBC, SUVmax decreased upon initial therapy.