Consensus on molecular imaging and theranostics in neuroendocrine neoplasms

Nuclear medicine plays an increasingly important role in the management neuroendocrine neoplasms (NEN). Somatostatin analogue (SSA)-based positron emission tomography/computed tomography (PET/CT) and peptide receptor radionuclide therapy (PRRT) have been used in clinical trials and approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). European Association of Nuclear Medicine (EANM) Focus 3 performed a multidisciplinary Delphi process to deliver a balanced perspective on molecular imaging and radionuclide therapy in well-differentiated neuroendocrine tumours (NETs). NETs form in cells that interact with the nervous system or in glands that produce hormones. These cells, called neuroendocrine cells, can be found throughout the body, but NETs are most often found in the abdomen, especially in the gastrointestinal tract. These tumours may also be found in the lungs, pancreas and adrenal glands. In addition to being rare, NETs are also complex and may be difficult to diagnose. Most NETs are non-functioning; however, a minority present with symptoms related to hypersecretion of bioactive compounds. NETs often do not cause symptoms early in the disease process. When diagnosed, substantial number of patients are already found to have metastatic disease. Several societies' guidelines address Neuroendocrine neoplasms (NENs) management; however, many issues are still debated, due to both the difficulty in acquiring strong clinical evidence in a rare and heterogeneous disease and the different availability of diagnostic and therapeutic options across countries. EANM Focus 3 reached consensus on employing ⁶⁸gallium-labelled somatostatin analogue ([⁶⁸Ga]Ga-DOTA-SSA)-based PET/CT with diagnostic CT or magnetic resonance imaging (MRI) for unknown primary NET detection, metastatic NET, NET staging/restaging, suspected extra-adrenal pheochromocytoma/paraganglioma and suspected paraganglioma. Consensus was reached on employing ¹⁸fluorine-fluoro-2-deoxyglucose ([¹⁸F]FDG) PET/CT in neuroendocrine carcinoma, G3 NET and in G1-2 NET with mismatched lesions (CT-positive/[⁶⁸Ga]Ga-DOTA-SSA-negative). Peptide receptor radionuclide therapy (PRRT) was recommended for second line treatment for gastrointestinal NET with [⁶⁸Ga]Ga-DOTA-SSA uptake in all lesions, in G1/G2 NET at disease progression, and in a subset of G3 NET provided all lesions are positive at [¹⁸F]FDG and [⁶⁸Ga]Ga-DOTA-SSA. PRRT rechallenge may be used for in patients with stable disease for at least 1 year after therapy completion. An international consensus is not only a prelude to a more standardised management across countries but also serves as a guide for the direction to follow when designing new research studies.