Peptide Receptor Radionuclide Therapy.

Abstract The concept of using a targeting molecule labeled with a diagnostic radionuclide for using positron emission tomography or single photon emission computed tomography imaging with the potential to demonstrate that tumoricidal radiation can be delivered to tumoral sites by administration of the same or a similar targeting molecule labeled with a therapeutic radionuclide termed “theranostics.” Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs (SSAs) is a well-established second/third-line theranostic treatment for somatostatin receptor-positive well-differentiated (neuro-)endocrine neoplasms (NENs). PRRT with 177Lu-DOTATATE was approved by the regulatory authorities in 2017 and 2018 for selected patients with low-grade well-differentiated gastroenteropancreatic (GEP) NENs. It improves progression-free survival as well as quality of life of GEP NEN patients. Favorable symptomatic and biochemical responses using PRRT with 177Lu-DOTATATE have also been reported in patients with functioning metastatic GEP NENs like metastatic insulinomas, Verner Morrison syndromes (VIPomas), glucagonomas, and gastrinomas and patients with carcinoid syndrome. This therapy might also become a valuable therapeutic option for inoperable low-grade bronchopulmonary NENs, inoperable or progressive pheochromocytomas and paragangliomas, and medullary thyroid carcinomas. First-line PRRT with 177Lu-DOTATATE and combinations of this therapy with cytotoxic drugs are currently under investigation. New radiolabeled somatostatin receptor ligands include SSAs coupled with alpha radiation emitting radionuclides and somatostatin receptor antagonists coupled with radionuclides.