HER2-Targeted Affibody Molecule 99mTc-ABH2 for Imaging HER2 Expression in Breast Cancer

PURPOSE: Accuracy in in vivo assessment of human epidermal growth factor receptor type 2 (HER2) status is crucial for predicting the response to HER2-targeted therapies in breast cancer. This study assessed the safety, feasibility, and diagnostic accuracy of 99mTc-ABH2, a reengineered affibody molecule with radionuclide labeling, for HER2 expression in breast cancer using SPECT/CT imaging, compared with 18F-FDG PET/CT. PATIENTS AND METHODS: Thirty-six patients suspected of primary breast cancer were enrolled in this prospective, single-center study from March to July in 2023. Each participant underwent SPECT/CT imaging with 99mTc-ABH2 SPECT/CT and 18F-FDG PET/CT. The imaging results were validated against immunohistochemistry and fluorescence in situ hybridization, employing visual scores and quantitative values for analysis. RESULTS: Optimal imaging contrast was observed around 2 hours postinjection of 99mTc-ABH2. Among the evaluated 27 patients with immunohistochemistry and fluorescence in situ hybridization findings, the 99mTc-ABH2 SPECT/CT visual evaluation displayed a sensitivity of 71.4%, specificity of 72.2%, and accuracy of 71.9%. Using an SUVmax cutoff of 2.32, the sensitivity, specificity, and accuracy for detecting HER2 status were 92.86%, 72.22%, and 81.25%, respectively. Notably, 99mTc-ABH2 precisely identified all immunohistochemistry (3+) tumors and showed increased uptake in bone and lymph node metastases. Meanwhile, 18F-FDG PET/CT showed no significant difference in uptake between HER2 (2+/3+) and HER2 (0/1+) tumors (P = 0.81). CONCLUSIONS: This study validated 99mTc-ABH2 SPECT/CT as a promising diagnostic tool for precise HER2 assessment. The robust sensitivity for immunohistochemistry (3+) tumors and the visualization of metastases highlight its diagnostic significance, potentially impacting patient outcomes positively.