Detection of HER2 expression using Tc-NM-02 nanobody in patients with breast cancer: a non-randomized, non-blinded clinical trial.

Background: Tc radiolabeled nanobody NM-02 (Tc-NM-02) is a novel single photon emission computed tomography (SPECT) probe with a high affinity and specificity for human epidermal growth factor receptor 2 (HER2). In this study, a clinical imaging trial was conducted to investigate the relationship between Tc-NM-02 uptake and HER2 expression in patients with breast cancer.

Methods: Thirty patients with pathologically confirmed breast cancer were recruited and imaged with both Tc-NM-02 SPECT/computed tomography (CT) and F-fluorodeoxyglucose (F-FDG) positron emission tomography (PET)/CT. According to the treatment conditions before recruitment, patients were divided into two groups, the newly diagnosed group (n = 24) and the treated group (n = 6). The maximal standard uptake value (SUV) of F-FDG and SUV and mean SUV (SUV) of Tc-NM-02 in the lesions were determined to analyze the relationship with HER2 expression.

Results: No meaningful relationship was observed between F-FDG uptake and HER2 expression in 30 patients with breast cancer. Tc-NM-02 uptake was positively correlated with HER2 expression in the newly diagnosed group, but no correlation was observed in the treated group. Tc-NM-02 uptake in HER2-positive lesions was lower in those with effective HER2-targeted therapy compared with the newly diagnosed group. Tc-NM-02 SPECT/CT detected brain and bone metastases of breast cancer with a different imaging pattern from F-FDG PET/CT. Tc-NM-02 showed no non-specific uptake in inflamed tissues and revealed intra- and intertumoral HER2 heterogeneity by SPECT/CT imaging in 9 of the 30 patients with breast cancer.

Conclusions: Tc-NM-02 SPECT/CT has the potential for visualizing whole-body HER2 overexpression in untreated patients, making it a promising method for HER2 assessment in patients with breast cancer.

Trial Registration: NCT04674722, Date of registration: December 19, 2020.