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

Haitao Miao; Yuyun Sun; Yizi Jin; Xichun Hu; Shaoli Song; Jian Zhang

doi:10.3389/fonc.2022.894767

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

Front Oncol. 2022 May 30:12:894767. doi: 10.3389/fonc.2022.894767. eCollection 2022.

Authors

Haitao Miao^{1

2}, Yuyun Sun^{1

3}, Yizi Jin^{1

2}, Xichun Hu^{1

2}, Shaoli Song^{1

3}, Jian Zhang^{1

2

4}

Affiliations

¹ Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
² Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
³ Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.
⁴ Phase I Clinical Trial Center, Fudan University Shanghai Cancer Center, Shanghai, China.

Abstract

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 ⁶⁸Ga-NOTA-MAL-MZHER2 (⁶⁸Ga-HER2) affibody PET/CT could determine the HER2 status of each lesion if there was a clinical need for it.

Methods: ⁶⁸Ga-HER2 affibody PET/CT was performed in breast cancer patients if HER2 status remained unclear after standard examinations (including bone scan, ¹⁸F-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. ⁶⁸Ga-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 ⁶⁸Ga-HER2 affibody tumor uptake was considered positive in 16 patients, negative in 7 patients, and equivocal in one patient. The heterogeneity of ⁶⁸Ga-HER2 affibody uptake was observed, with a maximal 8.5-fold difference within one patient and a maximal 11-fold difference between patients. ⁶⁸Ga-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: ⁶⁸Ga-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.

Keywords: 68Ga-HER2 affibody; HER2-positive; PET/CT; breast cancer; molecular imaging.