Current status and future prospects of PET-imaging applications in patients with gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs).

Abstract

Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) represent a heterogeneous group of rare neoplasms with increasing incidence over the last decades. Localization of GEP-NETs and their metastases is a vital component for the implementation of accurate and patient-tailored treatment strategies. Addressing this challenge requires the employment of multidisciplinary imaging approaches, with hybrid positron emission tomography/computed tomography (PET/CT) imaging techniques standing at the forefront of this effort. GEP-NETs exhibit several pathophysiologic characteristics, which can serve as highly specific molecular targets that can be effectively visualized and quantified by means of PET-radiopharmaceuticals, facilitating diagnosis, accurate staging and efficient monitoring of treatment response. Furthermore, the capability for whole-body, in-vivo, non-invasive characterization of the molecular heterogeneity of the disease, provides strong prognostic information, while enabling the selection of patients suitable for precision-based theranostic approaches. The dual tracer (18F-FDG & 68Ga-DOTA-peptides) PET/CT imaging approach is the current optimal diagnostic imaging strategy, since it enables tumor localization, accurate staging, non-invasive whole-body total tumor burden characterization of disease heterogeneity, while providing strong prognostic information and guidance towards treatment strategy. Moreover, 64Cu-DOTATATE has been recently approved by FDA for SSTRs positive NETs, promising substantial diagnostic and logistical benefits. Furthermore, 18F-DOPA offers diagnostic capabilities for serotonin-secreting GEP-NETs which are not characterized by cell-surface over-expression of somatostatin receptors (SSTRs) and cannot be seen on morphological imaging. In addition, PET/CT with agents targeting the expression of glucagon-like peptide-1 receptor (GLP-R1) should be considered in cases of clinical suspicion for insulinomas that cannot be detected by morphological imaging or STTRs PET/CT imaging.