Radionuclide-based pharmaceuticals for breast cancer imaging: state of the art

Breast cancer (BC) is a biologically heterogeneous disease, and no single imaging modality captures the full spectrum of phenotypes across all stages of the disease. This review summarizes advances in receptor-targeted nuclear imaging approaches that support patient stratification, treatment selection and response monitoring.

We provide a comprehensive review of preclinical and clinical studies of PET and SPECT radiopharmaceuticals targeting BC-relevant biomarkers on tumor cells and within the tumor microenvironment, with emphasis on clinical use cases, practical limitations and theranostic translational readiness. Conventional imaging modalities and [¹⁸F]FDG PET/CT remain central to staging but can be limited by poor specificity and reduced sensitivity for small lesions. Although anatomical (RECIST) and metabolic (PERCIST) response criteria remain central in routine response assessment, their application in BC can be challenging, particularly in bone-predominant disease and in the presence of marked inter-lesional heterogeneity. Receptor-mediated nuclear imaging enables non-invasive, whole-body phenotyping beyond biopsy and maps spatial heterogeneity. Clinical progress has been achieved for steroid receptors (ER/PR/AR), HER2, GRPR and SSTR2 imaging, and extends to stromal targets such as FAP (FAPI tracers). Emerging targets, including CXCR4, NTSR1, NPY1R and TROP-2, further broaden the theranostic landscape, particularly in settings where biomarker profiles are heterogeneous or evolve over time.

Multi-target imaging strategies may better address intra- and inter-lesional heterogeneity. Larger prospective cohorts are needed to define diagnostic performance, clinical relevance and theranostic value in BC.