Application of a Novel (68)Ga-HER2 Affibody PET/CT Imaging in Breast Cancer Patients

BACKGROUND: Breast cancer is a heterogeneous disease, and the human epidermal growth factor receptor 2 (HER2) expression may vary considerably between primary and metastatic lesions, or even within a single lesion. Repeated biopsies cannot always be performed. In this feasibility trial, we assessed whether a novel (68)Ga-NOTA-MAL-MZHER2 ((68)Ga-HER2) affibody PET/CT could determine the HER2 status of each lesion if there was a clinical need for it. METHODS: (68)Ga-HER2 affibody PET/CT was performed in breast cancer patients if HER2 status remained unclear after standard examinations (including bone scan, (18)F-FDG PET/CT, CT, and feasible biopsy). All available images for each patient were evaluated through an independent review of two committee-certified radiologists with nuclear medicine expertise. In case of discrepancy, adjudication by a third radiologist was performed as needed. All radiologists were blinded to the clinical information. RESULTS: Twenty-four patients were enrolled. (68)Ga-HER2 affibody PET/CT was requested by physicians due to the following reasons: 6 with multiple primary cancers, 13 with metastases not amenable to biopsy or repeated biopsy, 6 with inconsistent HER2 status between primary and metastatic lesions, and 4 with different HER2 status within different metastases. The final PET report revealed that the (68)Ga-HER2 affibody tumor uptake was considered positive in 16 patients, negative in 7 patients, and equivocal in one patient. The heterogeneity of (68)Ga-HER2 affibody uptake was observed, with a maximal 8.5-fold difference within one patient and a maximal 11-fold difference between patients. (68)Ga-HER2 affibody PET/CT demonstrated a high diagnostic accuracy in differentiating HER2-enriched breast cancer, with a sensitivity of 91.7% and a specificity of 84.6%, regardless of prior lines of anti-HER2 therapies. CONCLUSION: (68)Ga-HER2 affibody PET/CT imaging could provide valuable information on HER2 expression of each tumor in the body of patients, which may help in personalized clinical decision-making. Its value is now under systemic assessment.