The expression of human epidermal growth factor receptor 2 (HER2) is a critical biomarker for guiding precision therapy in HER2-positive cancers. However, conventional diagnostic approaches are invasive and fail to resolve the spatiotemporal heterogeneity of HER2 expression. Molecular imaging using HER2-targeted probes provides a noninvasive alternative, enabling quantitative assessment of HER2 status at the whole-body level. This capability supports critical clinical needs including early molecular subtyping, sensitive detection of metastases, and dynamic monitoring of treatment response. This review focuses on the rational design and engineering strategies of emerging HER2-targeted probes, highlighting key advances in probe architecture and functional optimization. We systematically evaluate how optimization strategies improve imaging contrast, metabolic stability, and targeting specificity. Despite considerable preclinical progress, the widespread clinical translation of these probes remains challenged by issues in scalable manufacturing, reproducible quality control, and regulatory validation. Addressing these application barriers represents a critical objective for future research to fully realize the potential of HER2-targeted molecular imaging in precision oncology.
Guo et al. (2026) studied this question.