Molecular Imaging in neuroendocrine neoplasias

Molecular imaging, which uses molecular targets due to the overexpression of specific peptide hormone receptors on the tumour surface, has become an indispensable diagnostic technique. Neuroendocrine neoplasms (NENs) especially differentiated NENs or neuroendocrine tumours (NETs) are a rare group of heterogeneous tumours, characterized by the expression of hormone receptors on the tumour cell surface. This property makes them receptive to diagnostic and therapeutic approaches (theranostics) using radiolabelled peptides. Amongst the known hormone receptors, somatostatin receptors (SSTR) are expressed on the majority of NETs and are therefore the most relevant receptors for theranostic approaches. Current research aims to medically upregulate their expression, while other focuses are on the use of different radiopeptides (64Cu and 67Cu) or somatostatin-antagonists instead of the established somatostatin agonists. The GLP-1 receptor is another clinically relevant target, as GLP-1-R imaging has become the new standard for the localisation of insulinomas. For staging and prognostic evaluation in dedifferentiated NENs, 18F-FDG-imaging is useful, but lacks a therapeutic counterpart. Further options for patients with insufficient expression of SSTR involve metaiodobenzylguanidine (MIBG) and the molecular target C-X-C motif chemokine receptor-4 (CXCR4). New targets such as the glucose-dependant insulinotropic polypeptide receptor (GIPR) and the fibroblast activation protein (FAP) have been identified in NENs recently and await further evaluation. For medullary thyroid cancer 18-F-DOPA imaging is standard, however this technique is rather second line for other NENs. In this area, the discovery of minigastrin, which targets the cholecystokinin-2 (CCK2) receptors in medullary thyroid carcinoma and foregut NENs, may improve future management. This review aims to provide an overview of the most commonly used functional imaging modalities for theranostics in NENs today and in the possible future.