Peptide Receptor Radionuclide Therapy with [(177)Lu]Lu-DOTA-TATE in Patients with Advanced GEP NENS: Present and Future Directions

SIMPLE SUMMARY: Neuroendocrine neoplasms have been usually described as infrequent tumors, but their incidence has been rising over time. [(177)Lu]Lu-DOTA-TATE (PRRT-Lu) was approved by the European Medicines Agency and by the Food and Drug Administration as the first radiopharmaceutical for peptide receptor radionuclide therapy in progressive gastroenteropancreatic NET. PRRT-Lu is considered a therapeutic option in progressive SSTR-positive NETs with homogenous SSTR expression. The NETTER-1 study demonstrated that PRRT-Lu yielded a statistically and clinically significant improvement in PFS as a primary endpoint (HR: 0.18, p < 0.0001), as well as a clinical trend towards improvement in OS. These results made scientific societies incorporate PRRT-Lu into their clinical guidelines; however, some questions still remain unanswered. ABSTRACT: This review article summarizes findings published in the last years on peptide receptor radionuclide therapy in GEP NENs, as well as potential future developments and directions. Unanswered questions remain, such as the following: Which is the correct dose and individual dosimetry? Which is the place for salvage PRRT-Lu? Whicht is the role of PRRT-Lu in the pediatric population? Which is the optimal sequencing of PRRT-Lu in advanced GEP NETs? Which is the place of PRRT-Lu in G3 NENs? These, and future developments such as inclusion new radiopharmaceuticals and combination therapy with different agents, such as radiosensitizers, will be discussed.