Molecular Imaging and Theranostics in Pancreatic Neuroendocrine Tumours: From a Luminous Present to an Even Brighter Future.

Abstract

The present issue starts with an accurate description of physiopathological premises underlying the mechanisms of uptake of several radiotracers that can be used, with main reference to those characterizing the presence of Somatostatin Receptors (SSTRs), expressed by different subtypes of PanNETs. In this paper, Cuccurullo et al. begins with the explanation of the ancillary role of 18FFluorodeoxyglucose (18F-FDG) [1]. In NETs, 18F-FDG may act mainly as a negative prognostic indicator, having capability to reveal dedifferentiated lesions in the restaging of individual patients with a critical clinical evolution. The reason for its infrequent indication is consequently connected with the favorable biological behavior of the majority of PanNETs, which are typically slow growing and express SSTRs according to their degree of differentiation. Therefore, using somatostatin analogs (SSA) labeled with gamma or positron emitters, SSTRs can be used not only as a target for both diagnosis and therapy, but also for a prognostic evaluation. Currently, the somatostatin theranostic model, based on diagnosis with radiotracers and a Peptide Receptor Radionuclide Therapy (PRRT) performed with a similar molecule radiolabeled with a β (or α, hopefully in the future) emitter, represents one of the most successful options for the targeted therapy. Although radio-labeled agonists usually provide efficient results, somatostatin antagonists (SS-ANTs) have been recently also proposed, being usable for imaging and therapy. The Cuccurullo’s paper also highlights the reasons why the theranostic model based on SSTRs doesn’t work in insulinoma, which scarcely express SSTR2 and SSTR5, wich are. the most important targets for the routinely used radiolabeled somatostatin analogues. Therefore, in patients with a suspicious of insulinoma, different radiotracers, such as 18F FluoroDOPA (18F-DOPA) or tracers targeting glucagon-like peptide-1 receptor, have to be preferred. However, it has to be pointed out that, although F-DOPA showed interesting results in patients with PanNETs, its role is currently considered secondary compared to somatostatin analogues, especially because of the lack of a theranostic model.