From Bench to Bedside: A Critical Appraisal of Somatostatin Receptor Antagonists in the Theranostic Management of Neuroendocrine Neoplasms

Abstract

Neuroendocrine neoplasms are increasingly assessed using somatostatin receptor (SSTR) antagonists as an alternative to conventional agonists in molecular imaging and targeted radiopharmaceutical therapy. Radiolabeled SSTR antagonists, such as [68Ga]Ga-NODAGA-JR11 and [68Ga]Ga-NODAGA-LM3, have demonstrated higher tumor-to-background ratios and enhanced lesion detection in several studies, particularly in hepatic metastases. Therapeutically, radiolabeled antagonists such as [177Lu]Lu-DOTA-LM3 and [177Lu]Lu-DOTA-JR11 have shown promising tumor uptake and dosimetry profiles, including in patients with progressive disease after prior therapies. However, current evidence is largely derived from early-phase and heterogeneous studies. Increased hematologic toxicity and the absence of prospective evidence demonstrating a survival benefit remain key limitations. This review provides a critical synthesis of the available data, highlighting both the potential advantages and the unresolved challenges of SSTR antagonist–based imaging and therapy in neuroendocrine neoplasms.