A further distinction-in about 25% of patients-involves the ability of the tumors to secrete hormones leading to specific symptoms, separating them into functioning and non-functioning tumors. Well-differentiated NENs are classified as grade 1, 2, or 3 neuroendocrine tumors (NETs), based on the mitotic counts and Ki67 index, while poorly differentiated NENs are categorized as grade 3 neuroendocrine carcinomas (NEC). The classification of NENs depends on their origin and extension, with the grading being based on histological differentiation. However, incidental detection at an early stage of disease has been reported due to improved diagnostic procedures. In about half of the patients, the diagnosis is established at a non-resectable stage due to unspecific clinical syndromes and slow tumor growth with late symptomatic manifestation. Neuorendocrine neoplasms (NENs) are rare tumors with increasing prevalence deriving from neuroendocrine cells localized mainly in the intestine, pancreas and lung. Molecular imaging is an emerging field that improves the management of NENs. Other new targets involve the fibroblast activation protein and the cholecystokinin-2 receptors, where the ligand minigastrin opens new possibilities for the management of medullary thyroid carcinoma. For dedifferentiated NENs, new molecular targets such as the C-X-C motif chemokine-receptor-4 have been evaluated. Targeting the glucagon-like peptide-1 receptor by exendin-4 has a high sensitivity in localizing insulinomas. In addition to the established imaging technique of targeting somatostatin receptors, several alternative radioligands have been developed. The discovery of molecular targets due to the overexpression of specific peptide hormone receptors on the NEN’s surface has triggered the development of multiple radionuclide imaging modalities. This review aims at giving an overview on contemporary imaging methods and providing an outlook on current progresses. The search for the optimal imaging technique has triggered rapid development in the field. Accurate imaging is crucial for correct diagnosis, staging, and therapy of neuroendocrine neoplasms (NENs).
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