Molecular Imaging of Neuroendocrine Neoplasms

The key for molecular imaging is the use of a radiotracer with a radioactive and a functional component. While the functional component targets a specific feature of the tumor, the radioactive component makes the target visible. Neuroendocrine neoplasms (NEN) are a diverse group of rare tumors that arise from neuroendocrine cells found mainly in the gastroenteropancreatic system, lung, thyroid, and adrenal glands. They are characterized by the expression of specific hormone receptors on the tumor cell surface, which makes them ideal targets for radiolabeled peptides. The most commonly expressed hormone receptors on NEN cells are the somatostatin receptors. They can be targeted for molecular imaging with various radiolabeled somatostatin analogs, but also with somatostatin antagonists, which have shown improved imaging quality. 18F-DOPA imaging has become a second-line imaging modality in NENs, with the exception of the evaluation of advanced medullary thyroid carcinoma. Alternatives for NENs with insufficient somatostatin receptor expression due to poor differentiation involve targeting glucose metabolism, which can also be used for prognosis. For the localization of the often-small insulinoma, glucagon-like peptide-1 (GLP-1) receptor imaging has become the new standard. Other alternatives involve metaiodobenzylguanidine and the molecular target C-X-C motif chemokine receptor-4. In addition, new radiopeptides targeting the fibroblast activation protein, the glucose-dependent insulinotropic polypeptide receptor and cholecystokinin-2 receptors have been identified in NENs and await further evaluation. This mini-review aims to provide an overview of the major molecular imaging modalities currently used in the field of NENs, and also to provide an outlook on future developments.