Imaging of Neuroendocrine Tumors

Neuroendocrine tumors (NETs) are rare neoplasms, which are characterized by the presence of neuroamine uptake mechanisms and/or peptide receptors at the cell membrane and these features constitute the basis of the clinical use of specific radiolabeled ligands, both for imaging and therapy. Radiolabeled metaiodobenzylguanidine (MIBG) was the first radiopharmaceutical used to specifically depict and localize catecholamine-secreting tumors (pheochromocytomas, paragangliomas, and neuroblastomas) and is still regarded as a first-choice imaging technique for diagnosis and follow-up; in patients with malignant disease, MIBG scintigraphy is an essential step to select patients for ¹³¹I-MIBG therapy. Scintigraphy with ¹¹¹In- or ^99mTc-labeled somatostatin analogs has become the main imaging technique for NETs, particularly those expressing a high density of somatostatin receptors, such as gastroenteropancreatic tumors; this procedure is used routinely for localizing the primary tumor, evaluating disease extension, monitoring the effect of treatment and for selecting patients for radioreceptor therapy. Since the recent development of hybrid machines, it has been possible to obtain images that simultaneously hold both anatomic (computed tomography [CT]) and functional (single-photon emission computed tomography [SPECT] or positron emission tomography [PET]) information, with great impact on diagnostic accuracy. Significant improvements have been made during the past few years with the development of highly specific radiopharmaceuticals for PET studies that reflect the different metabolic pathways of NETs, such as glucose metabolism (¹⁸F-fluorodeoxyglucose), the uptake of hormone precursors (¹¹C-5-hydroxytryptophan, ¹¹C- or ¹⁸F-dihydroxyphenylalanine, ¹⁸F-fluorodopamine), the expression of receptors (⁶⁸Ga-labeled somatostatin analogs), as well as the synthesis, storage, and release of hormones (¹¹C-hydroxyephedrine and others). Among these radiopharmaceuticals, ⁶⁸Ga-labeled somatostatin analogs are increasingly used in specialized centers in Europe for PET and PET/CT imaging and show very promising results with high diagnostic sensitivity. New somatostatin analogs with different receptor affinity as well as other peptides are currently under investigation and will further improve our diagnostic and therapeutic capabilities in the future.