Advances in multi-dimensional targeting probes for precision medicine of breast cancer.

Breast cancer (BC) remains the most frequently diagnosed cancer and the second leading cause of cancer-related mortality among women worldwide. Medical imaging is essential in the diagnosis and management of BC, delivering crucial information about tumor location, heterogeneity, and metastatic progression. Nuclear medicine imaging offers non-invasive functional assessment through probes, which capture biological characteristics of tumors more effectively than conventional structural imaging modalities such as CT or MRI. The identification of specific molecular targets has become pivotal for accurate tumor subtyping, prognosis assessment, and tailoring effective therapies. In this review, these molecular targets are classified according to a three-dimensional spatial framework of BC, encompassing (1) intracellular metabolic processes, (2) cell-surface receptor expression, and (3) the extracellular TME. Through multi-dimensional targeting approaches from intracellular processes to microenvironmental networks, nuclear medicine imaging decodes BC biology: metabolism imaging reveals core cellular functions, receptor imaging identifies actionable therapeutic targets and evaluates molecular expression levels, and TME imaging elucidates complex microenvironmental interactions. Collectively, this spatially-informed targeting strategy allows for the non-invasive evaluation of therapeutic targets, assessment of tumor heterogeneity, and dynamic monitoring of treatment response. Furthermore, these advances are increasingly extending beyond diagnostics toward theranostic applications, where diagnostic probes are paired with therapeutic radionuclides to enable image-guided radioligand therapy. By consolidating current knowledge and outlining future directions, this review aims to inform both clinical practice and the development of next-generation imaging and theranostic platforms in precision oncology.