Santo Giulia, di Santo Gianpaolo, Cicone Francesco, Virgolini Irene
Department of Nuclear Medicine, Medical University of Innsbruck, Innsbruck, Austria.
Department of Experimental and Clinical Medicine, "Magna Graecia" University of Catanzaro, Catanzaro, Italy.
J Neuroendocrinol. 2025 Mar;37(3):e70013. doi: 10.1111/jne.70013. Epub 2025 Mar 10.
First isolated by Brazeau et al. in 1972, somatostatin (SST) is a neuropeptide known for regulating various signaling pathways through its specific cell surface receptors. Somatostatin receptors (SSTRs) comprise a family of five G protein-coupled receptors that are widely distributed across the human body and are expressed by various tumor types. The growing understanding of their clinical potential led to the introduction of both cold and radiolabeled somatostatin analogs (SSAs), which have revolutionized the management of several cancers, especially neuroendocrine tumors. As a direct consequence, advances in peptide receptor radionuclide therapy (PRRT) over the last 30 years led to the approval of Lu-DOTATATE for the treatment of gastroenteropancreatic neuroendocrine tumors (GEPNETs). Theoretically, any cancer patients whose tumors express SSTR, as demonstrated in vivo through SSTR-based molecular imaging, could be candidates for PRRT, especially those with limited treatment options. However, evidence on the efficacy of PRRT in non-GEPNET SSTR-expressing tumors is limited, and mainly derived from small retrospective studies. Given the limited therapeutic options for advanced/metastatic patients, there is a clear need for randomized trials to formally approve PRRT with SSAs for patients who may benefit from this treatment, particularly in certain types of neuroendocrine neoplasms such as lung carcinoids, paragangliomas, and meningiomas, where high rates of disease control (up to 80%) can be achieved. In addition, emerging evidence supports the potential of combination therapies, alpha emitters, and non-SSTR-based radionuclide therapy in tumors beyond GEPNET. This review aims to provide a comprehensive overview of PRRT's role in cancers beyond GEPNET, exploring new possibilities and future directions for most SSTR highly expressing tumors.
生长抑素（SST）于1972年首次由布拉佐等人分离出来，是一种神经肽，以通过其特定的细胞表面受体调节各种信号通路而闻名。生长抑素受体（SSTRs）由五个G蛋白偶联受体组成的家族，广泛分布于人体各处，并由多种肿瘤类型表达。对其临床潜力的日益了解导致了冷和放射性标记的生长抑素类似物（SSAs）的引入，这彻底改变了几种癌症的治疗方式，尤其是神经内分泌肿瘤。直接的结果是，过去30年中肽受体放射性核素治疗（PRRT）的进展导致镥[177Lu]奥曲肽被批准用于治疗胃肠胰神经内分泌肿瘤（GEPNETs）。从理论上讲，任何肿瘤表达SSTR的癌症患者，如通过基于SSTR的分子成像在体内所证实的，都可能是PRRT的候选者，尤其是那些治疗选择有限的患者。然而，关于PRRT在非GEPNET SSTR表达肿瘤中的疗效证据有限，且主要来自小型回顾性研究。鉴于晚期/转移性患者的治疗选择有限，显然需要进行随机试验，以正式批准将SSAs用于可能从这种治疗中受益的患者的PRRT，特别是在某些类型的神经内分泌肿瘤中，如肺类癌、副神经节瘤和脑膜瘤，在这些肿瘤中可以实现高达80%的疾病控制率。此外，新出现的证据支持联合治疗、α发射体以及非SSTR基放射性核素治疗在GEPNET以外肿瘤中的潜力。本综述旨在全面概述PRRT在GEPNET以外癌症中的作用，探索大多数SSTR高表达肿瘤的新可能性和未来方向。
