Expanding the therapeutic horizon of ¹⁷⁷Lu-DOTATATE: a review of current evidence

Neuroendocrine tumors (NETs) are a heterogenous group of neoplasms originating from neuroendocrine cells, most frequently found in the gastrointestinal tract and pancreas. A defining feature of NETs is the overexpression of somatostatin receptors (SSTRs), particularly subtype 2 (SSTR2), which is the primary target for both diagnostic imaging and therapeutic interventions. Peptide receptor radionuclide therapy (PRRT) using ¹⁷⁷Lu-DOTATATE, a radiolabeled somatostatin analog, has emerged as a transformative alternative for patients with advanced or progressive well-differentiated NETs. Considering that SSTR expression is also present in various other tumors-including pheochromocytomas, paragangliomas, meningiomas, and medullary thyroid carcinomas-there is increasing interest in expanding the use of PRRT to other SSTR-positive malignancies. This review aimed to present evidence, explore ongoing clinical research, and highlight emerging directions for ¹⁷⁷Lu-DOTATATE therapy beyond gastroenteropancreatic NETs.