SSTR

Somatostatin receptor (SSTR) refers to a family of five G protein-coupled receptors (SSTR1–SSTR5) that bind the neuropeptide somatostatin and, to a lesser extent, cortistatin. They couple to Gi/o proteins, inhibiting adenylyl cyclase, reducing cyclic AMP, modulating calcium channels, and suppressing secretion in target cells. SSTRs are expressed in a wide range of tissues, including the pituitary, brain, gastrointestinal tract, and pancreas. Among the subtypes, SSTR2 is commonly the most abundant in neuroendocrine tumors and is a primary target for imaging and therapy, while SSTR1, SSTR3, SSTR4, and SSTR5 have more variable tissue distributions.

In clinical practice, SSTR expression is used for diagnostic and therapeutic purposes. Diagnostic imaging employs radiolabeled somatostatin analogs, such as 68Ga-DOTATATE, 68Ga-DOTATOC, and 68Ga-DOTANOC, in PET/CT to visualize SSTR-expressing lesions and guide management, including eligibility for receptor-targeted therapies. Therapeutically, somatostatin analogs such as octreotide and lanreotide help control hormone-related symptoms and can slow tumor progression in many neuroendocrine tumors. Radioligand therapy (RLT) with radionuclide-labeled analogs like 177Lu-DOTATATE and 177Lu-DOTATOC delivers targeted radiation to SSTR-expressing cells and is approved for certain advanced NETs.

Limitations include variability in receptor expression and tumor biology; not all tumors express SSTRs, and responses to therapy vary. Treatments may cause side effects such as gallstone formation and gastrointestinal disturbances with analogs, or hematologic and renal toxicity with RLT. SSTR expression has also been observed in other neoplasms and some inflammatory conditions, broadening potential diagnostic considerations.