Molecular imaging of neuroendocrine tumors: Current applications and future trends.

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, [68Ga]DOTATATE is the first line agent. In pheochromocytoma, paraganglioma, and neuroblastomas [131I]MIBG can also be considered for imaging. [18F]FDOPA is mainly used for midgut NETs but is second line if access to [68Ga]DOTATATE is difficult. In insulinomas, glucagon like peptide-1 receptor agents can be considered with [68Ga]DOTATATE. In medullary thyroid carcinomas, [18F]FDOPA is preferred with or without [68Ga]DOTATATE imaging. In poorly-differentiated NEN/NEC, non-specific agents such as [18F]Fluoro-2-deoxy-d-glucose and [68Ga]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 [68Ga]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.