Radiolabeled Somatostatin Analogues for Diagnosis and Treatment of Neuroendocrine Tumors

Abstract

Neuroendocrine neoplasms (NENs) are rare and heterogeneous tumors that require multidisciplinary discussion for optimal care. The theranostic approach (DOTA peptides labelled with [68Ga] for diagnosis and with 90Y or 177Lu for therapy) plays a crucial role in the management of NENs to assess disease extension and as a criteria for peptide receptor radionuclide therapy (PRRT) eligibility based on somatostatin receptor (SSTR) expression. On the diagnostic side, [68Ga]Ga-DOTA peptides PET/CT (SSTR PET/CT) is the gold standard for imaging well-differentiated SSTR-expressing neuroendocrine tumors (NETs). [18F]FDG PET/CT is useful in higher grade NENs (NET G2 with Ki-67 > 10% and NET G3; NEC) for more accurate disease characterization and prognostication. Promising emerging radiopharmaceuticals include somatostatin analogues labelled with 18F (to overcome the limits imposed by 68Ga), and SSTR antagonists (for both diagnosis and therapy). On the therapeutic side, the evidence gathered over the past two decades indicates that PRRT is to be considered as an effective and safe treatment option for SSTR-expressing NETs, and is currently included in the therapeutic algorithms of the main scientific societies. The positioning of PRRT in the treatment sequence, as well as treatment personalization (e.g., tailored dosimetry, re-treatment, selection criteria, and combination with other alternative treatment options), is warranted in order to improve its efficacy while reducing toxicity. Although very preliminary (being mostly hampered by lack of methodological standardization, especially regarding feature selection/extraction) and often including small patient cohorts, radiomic studies in NETs are also presented. To date, the implementation of radiomics in clinical practice is still unclear. The purpose of this review is to offer an overview of radiolabeled SSTR analogues for theranostic use in NENs.

Chemotherapy in Well Differentiated Neuroendocrine Tumors (NET) G1, G2, and G3: A Narrative Review

“…TEM and CAPTEM can also be combined with PRRT to improve activity and cover the latency of PRRT effect onset [ 55 ]. Recently, the Australasian Gastrointestinal Trials Group (AGITG) CONTROL NET study, a randomized (2:1) phase II open-label trial of 177Lu-Octreotate PRRT in combination with CAPTEM, enrolled 28 patients with panNET: 19 were randomized to receive CAPTEM + PRRT, while 9 received CAPTEM alone [ 25 ].…”

Evaluating Prognosis of Gastrointestinal Metastatic Neuroendocrine Tumors: Constructing a Novel Prognostic Nomogram Based on NETPET Score and Metabolic Parameters from PET/CT Imaging

“…Numerous studies have reported that PET-CT imaging using 68 Ga-labeled somatostatin analogs ( 68 Ga-SSA) as contrast agents exhibit exceptionally high specificity and sensitivity in the diagnosis of NETs [33][34][35]. Additionally, 68 Ga PET/CT can serve as a valuable tool in guiding the management of Peptide Receptor Radionuclide Therapy (PRRT) and Somatostatin Analogues (SSA) [36]. Therefore, it plays a critical role in the comprehensive management of NETs.…”

Typical Zollinger-Ellison syndrome-atypical location of gastrinoma and absence of hypergastrinemia: A case report and review of literature

“…According to the European guidelines, SSTR PET is preferred over octreoscan for the diagnostic workup of NETs[ 20 , 21 ]. 18F is the most widely employed radionuclide in PET owing to its chemical, physical, and nuclear properties, which render it ideal for peptide-based imaging[ 22 ]. Despite these advantages, until recently, only a few radiotracers for SSTR labeled with 18F have been described[ 23 , 24 ].…”