Wang Ivan E, SaTsu Helen A, Brooks Allen F, Werner Rudolf A, Rowe Steven P, Scott Peter J H, Viglianti Benjamin L
Department of Radiology, University of Michigan, Ann Arbor MI 48109 USA.
Department of Nuclear Medicine, LMU University Hospital 80336 Munich, Germany.
Diagn Interv Imaging. 2025 May 21. doi: 10.1016/j.diii.2025.05.005.
The prevalence of neuroendocrine neoplasms (NEN), which include neuroendocrine tumors (NET) and neuroendocrine carcinomas (NEC), has increasing during recent years. The approval of diagnostic single-photon emission computed tomography and positron emission tomography imaging agents for NEN is an important factor in pushing the development of additional agents using new targets to develop patient-specific, targeted, radiopharmaceuticals. Numerous NEN-specific targets exist, including somatostatin receptors, norepinephrine transport substrates, amino acid transport substrates, and glucagon-like peptide-1 receptor analogues, as well as non-specific targets, such as glucose metabolism. Additionally, there are targets that can be used in combination with current agents to further personalize NEN imaging. In well-differentiated gastroenteropancreatic NET, [Ga]DOTATATE is the first line agent. In pheochromocytoma, paraganglioma, and neuroblastomas [I]MIBG can also be considered for imaging. [F]FDOPA is mainly used for midgut NETs but is second line if access to [Ga]DOTATATE is difficult. In insulinomas, glucagon like peptide-1 receptor agents can be considered with [Ga]DOTATATE. In medullary thyroid carcinomas, [F]FDOPA is preferred with or without [Ga]DOTATATE imaging. In poorly-differentiated NEN/NEC, non-specific agents such as [F]Fluoro-2-deoxy-d-glucose and [Ga]fibroblast activation protein inhibitor-04 can be used if somatostatin imaging is insufficient. Urokinase plasminogen activator receptor targeting has been used as a method for risk stratification and can be used in combination with [Ga]DOTATATE. The use of somatostatin receptor antagonists, bombesin receptor 2, C-X-C motif chemokine receptor-4, and glucose-dependent insulinotropic polypeptide receptor agents are currently in development - with all of them requiring further studies to determine their potential utility. This review analyzes the current landscape of NEN imaging and discusses the emerging agents that can potentially contribute to NEN imaging in the future.
神经内分泌肿瘤（NEN）包括神经内分泌瘤（NET）和神经内分泌癌（NEC），近年来其发病率呈上升趋势。用于NEN的诊断性单光子发射计算机断层扫描和正电子发射断层扫描成像剂的获批，是推动利用新靶点开发更多药物以研制针对患者的靶向放射性药物的一个重要因素。存在许多NEN特异性靶点，包括生长抑素受体、去甲肾上腺素转运底物、氨基酸转运底物和胰高血糖素样肽-1受体类似物，以及非特异性靶点，如葡萄糖代谢。此外，还有一些靶点可与现有药物联合使用，以进一步实现NEN成像的个性化。在高分化胃肠胰神经内分泌瘤中，[镓] DOTATATE是一线药物。在嗜铬细胞瘤、副神经节瘤和神经母细胞瘤中，[碘] MIBG也可用于成像。[氟] FDOPA主要用于中肠神经内分泌瘤，但如果难以获得[镓] DOTATATE，则作为二线药物。在胰岛素瘤中，胰高血糖素样肽-1受体药物可与[镓] DOTATATE联合使用。在甲状腺髓样癌中，[氟] FDOPA在有或没有[镓] DOTATATE成像的情况下都是首选。在低分化NEN/NEC中，如果生长抑素成像不足，可使用[氟]氟代脱氧葡萄糖和[镓]成纤维细胞激活蛋白抑制剂-04等非特异性药物。尿激酶型纤溶酶原激活物受体靶向已被用作一种风险分层方法，可与[镓] DOTATATE联合使用。生长抑素受体拮抗剂、胃泌素释放肽受体2、C-X-C基序趋化因子受体-4和葡萄糖依赖性促胰岛素多肽受体药物目前正在研发中——所有这些都需要进一步研究以确定其潜在用途。本综述分析了NEN成像的当前现状，并讨论了未来可能有助于NEN成像的新兴药物。
