The Role of [177Lu] Lu-Satoreotide Tetraxetan in Somatostatin Receptor-Positive Neuroendocrine Tumors.

Peptide receptor radionuclide therapy (PRRT) targeting the somatostatin receptor with receptor agonists has emerged as a key treatment in the management of well-differentiated neuroendocrine tumors (NETs). The therapeutic efficacy of these agents has traditionally been attributed to receptor-mediated internalization of the radiolabeled peptide into tumor cells. In contrast, somatostatin receptor (SSTR) antagonists bind to the receptor without undergoing significant internalization. Despite this theoretical limitation, accumulating preclinical and clinical evidence supports the therapeutic utility of SSTR antagonists. These agents have been shown to bind to a greater number of receptor sites and exhibit prolonged tumor retention, properties that may enhance both imaging sensitivity and therapeutic efficacy. Among the antagonists studied, [¹⁷⁷Lu]Lu-satoreotide tetraxetan is the most extensively investigated to date. In this article, we review both preclinical and clinical data evaluating the efficacy and safety of [¹⁷⁷Lu]Lu-satoreotide tetraxetan in the treatment of neuroendocrine tumors. We also provide a brief overview of other SSTR antagonists currently under investigation.