Molecular imaging in neuroendocrine tumors: Recent advances, controversies, unresolved issues, and roles in management

Purpose of review: The purpose is to review recent advances in molecular imaging of neuroendocrine tumors (NETs), discuss unresolved issues, and review how these advances are affecting clinical management. Recent findings: Molecular imaging of NETs underwent a number of important changes in the last few years, leading to some controversies, unresolved issues, and significant changes in clinical management. The most recent changes are reviewed in this article. Particularly important is the rapid replacement in somatostatin receptor scintigraphy of 111In-diethylenetriamine penta-acetic acid-single-photon emission computed tomography/computed tomography (CT) by ⁶⁸Ga-fluorodopa(F-D)PA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-peptide-PET/CT imaging, which is now approved in many countries including the USA. Numerous studies in many different types of NETs demonstrate the greater sensitivity of ⁶⁸Ga-DOTA-peptide PET/CT, its high specificity, and its impact on management. Other important developments in somatostatin receptor scintigraphy/molecular imaging include demonstrating the prognostic value of both ⁶⁸Ga-DOTA-peptide PET/CT and ¹⁸F-fluoro-deoxyglucose PET/CT; how their use can be complementary; comparing the sensitivities and usefulness of ⁶⁸Ga-DOTA-peptide PET/CT and ¹⁸F-FDOPA PET/CT; introducing new linkers and radiolabeled ligands such as ⁶⁴Cu-DOTA-peptides with a long half-life, enhancing utility; and the introduction of somatostatin receptor antagonists which show enhanced uptake by NETs. In addition, novel ligands which interact with other receptors (GLP-1, bombesin, cholecystokinin, gastric inhibitory polpeptide, integrin, chemokines) are described, which show promise in the imaging of both NETs and other tumors. Summary: Molecular imaging is now required for all aspects of the management of patients with NETs. Its results are essential not only for the proper diagnostic management of the patient, but also for assessing whether the patient is a candidate for peptide receptor radionuclide therapy with 177Lu and also for providing prognostic value.