New PET Radiotracers for the Imaging of Neuroendocrine Neoplasms

Neuroendocrine neoplasms (NEN) are a heterogeneous group of tumours derived from cells of neuroendocrine origin and can potentially arise everywhere in the human body. The diagnostic assessment of NEN can be performed using a variety of PET radiopharmaceuticals. Well-differentiated NEN (NET) present a high expression of SSTR (somatostatin receptors) and can therefore be studied with 68Ga-DOTA-peptides ([68Ga]Ga-DOTANOC, [68Ga]Ga-DOTATOC, [68Ga]Ga-DOTATATE). Current guidelines recommend the use of SSTR imaging to assess disease extension at staging/restaging, follow-up, assessment of response to therapy and selection of patients who may benefit from radionuclide therapy (PRRT). [18F]F-FDG is used for the assessment of high-grade tumours (high-grade G2, G3 and NEC) and in every case, there is one or more mismatched lesions between diagnostic CT (positive) and SSTR-PET/CT (negative). [18F]F-DOPA is currently used for the assessment of medullary thyroid carcinoma, neuroblastoma, primary pheochromocytoma and abdominal paraganglioma. In recent years, however, several new tracers were designed exploiting the many potential targets of the neuroendocrine cell and were employed in clinical trials for both imaging and therapy. Currently, the real-life clinical impact of these tracers is still mostly not known; however, the favourable biodistribution (e.g. [68Ga]Ga-FAPI, SSTR antagonists) and the possibility to use new theranostic pairs may provide novel diagnostic as well as therapeutic options (e.g. [68Ga]Ga-PSMA, [64Cu]Cu-SARTATE, [68Ga]Ga-CXCR4) for NEN patients.