FROM DISCOVERY SCIENCE TO THE CLINIC - HERITABLE ENDOCRINE CANCERS AND RELATED DISORDERS: Functional imaging in hereditary endocrine neoplasms: evolving modalities and clinical implications.

Hereditary endocrine neoplastic syndromes require structured, lifelong surveillance owing to their multisystem involvement, variable penetrance, and high risk of multifocal and metastatic disease. Functional imaging (FI) is now integral to their management, providing molecular characterisation that complements conventional anatomical modalities and frequently enables earlier or more specific lesion detection. This review summarises current FI approaches across major hereditary syndromes, including multiple endocrine neoplasia types 1-4, von Hippel-Lindau disease, and hereditary paraganglioma-phaeochromocytoma syndromes with emphasis on radiotracer selection, genotype-phenotype correlations and implications for clinical practice. The performance and biological rationale for established radiotracers, including 18F-FDG, 68Ga-DOTATATE, 18F-DOPA, and choline-based PET agents and emerging probes, is described. Increasing evidence supports genotype-directed imaging algorithms, particularly in HPPSs, where molecular subtype predicts tracer avidity and guides theranostic strategies. The expanding theranostic framework, anchored in somatostatin receptors and norepinephrine transporter-directed radiopharmaceuticals, has reshaped treatment pathways for advanced and metastatic disease. Implementation challenges persist, including variable global access, high costs, workforce limitations, and concerns regarding cumulative radiation exposure during decades of surveillance. Technical constraints related to spatial resolution, partial-volume effects, and motion artefact continue to limit the sensitivity of small-lesion detection. Emerging approaches incorporating radiomics and artificial intelligence offer opportunities to enhance lesion characterisation, infer genetic subtype, and improve prognostication. Advancing FI in hereditary endocrine neoplasia will require genetically informed surveillance protocols, harmonised imaging standards, and equitable access to specialised modalities. Collectively, these developments have the potential to refine risk stratification, improve treatment selection, and optimise long-term outcomes for individuals with hereditary endocrine malignancies.