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.

Keywords: PRRT; [Ga]-DOTA peptides PET/TC; neuroendocrine; somatostatin.

Figure 1

[⁶⁸Ga]Ga-DOTA-NOC and [¹⁸F]FDG mip (a,b) and transaxially fused (c,d) PET/CT images of a patient with a pancreatic G2 NET (Ki-67 = 12%). High SSTR expression is observed in the primary pancreatic body lesion (a,c), while significant [¹⁸F]FDG uptake (b,d) is detected at the liver metastatic level (SSTR-negative). This case shows the potential of the double-tracer PET/CT approach in demonstrating NET de-differentiation.