Combination of Cross-Sectional and Molecular Imaging Studies in the Localization of Gastroenteropancreatic Neuroendocrine Tumors

Abstract

Molecular imaging modalities exploit aspects of neuroendocrine tumors (NET) pathophysiology for both diagnostic imaging and therapeutic purposes. The characteristic metabolic pathways of NET determine which tracers are useful for their visualization. In this review, we summarize the diagnostic value of all available molecular imaging studies, present data about their use in daily practice in NET centers globally, and finally make recommendations about the appropriate use of those modalities in specific clinical scenarios. Somatostatin receptor scintigraphy (SRS) continues to have a central role in the diagnostic workup of patients with NET, as it is also widely available. However, and despite the lack of prospective randomized studies, many NET experts predict that Gallium-68 (⁶⁸Ga)-DOTA positron emission tomography (PET) techniques may replace SRS in the future, not only because of their technical advantages, but also because they are superior in patients with small-volume disease, in patients with skeletal metastases, and in those with occult primary tumors. Carbon-11 (¹¹C)-5-hydroxy-L-tryptophan (5-HTP) PET and ¹⁸F-dihydroxyphenylalanine (¹⁸F-DOPA) PET are new molecular imaging techniques of limited availability, and based on retrospective data, their sensitivities seem to be inferior to that of ⁶⁸Ga-DOTA PET. Glucagon-like-peptide-1 (GLP-1) receptor imaging seems promising for localization of the primary in benign insulinomas, but is currently available only in a few centers. Fluorine-18 (¹⁸F)-fluorodeoxyglucose (¹⁸F-FDG) PET was initially thought to be of limited value in NET, due to their usually slow-growing nature. However, according to subsequent data, ¹⁸F-FDG PET is particularly helpful for visualizing the more aggressive NET, such as poorly differentiated neuroendocrine carcinomas, and well-differentiated tumors with Ki67 values >10%. According to limited data, ¹⁸F-FDG-avid tumor lesions, even in slow-growing NET, may indicate a more aggressive disease course. When a secondary malignancy has already been established or is strongly suspected, combining molecular imaging techniques (e.g. ¹⁸F-FDG PET and ⁶⁸Ga-DOTA PET) takes advantage of the diverse avidities of different tumor types to differentiate lesions of different origins. All the above-mentioned molecular imaging studies should always be reviewed and interpreted in a multidisciplinary (tumor board) meeting in combination with the conventional cross-sectional imaging, as the latter remains the imaging of choice for the evaluation of treatment response and disease follow-up.