Somatostatin Receptor Expression and Theranostic Applications Across Non-Neuroendocrine Tumors: A Molecular-to-Clinical Review.

Somatostatin receptor (SSTR)-targeted imaging and therapy are established approaches for neuroendocrine tumors, but accumulating evidence indicates that SSTRs are also expressed in various non-neuroendocrine tumors. This review aimed to summarize their expression patterns, imaging characteristics, and theranostic potential. Published evidence was reviewed for central nervous system tumors, head and neck cancers, thyroid carcinoma, lung cancer, breast cancer, lymphoma, and melanoma, with particular attention to the cellular localization of SSTR expression and the mechanisms underlying radiotracer uptake. Meningioma, non-keratinizing nasopharyngeal carcinoma, and selected estrogen receptor-positive breast cancers show relatively prominent tumor-cell SSTR expression. In several other malignancies, SSTR expression may predominantly involve tumor-associated macrophages, endothelial cells, fibroblasts, or other stromal components. Imaging findings are heterogeneous across and within tumor types. Preliminary studies suggest that peptide receptor radionuclide therapy may provide clinical benefit in selected patients with SSTR-positive non-neuroendocrine tumors, although the available evidence remains limited and largely non-prospective. Further studies integrating quantitative molecular imaging, spatial pathology, and molecular profiling are needed to clarify receptor biology, establish patient-selection criteria, and define the clinical role of SSTR-targeted theranostics beyond neuroendocrine tumors.