Peptide receptor radionuclide therapy with 177Lu-DOTATATE (LUTATHERA®) is a novel treatment approved in 2018 that utilizes an injectable, radioactive form of the somatostatin analog DOTATATE to deliver internal, targeted radiation therapy. It is approved for all gastroenteropancreatic (GEP)-NET patients with inoperable, metastatic disease who progress on first-line somatostatin receptor therapy with octreotide or lanreotide. It is the therapeutic analog of 68Ga-DOTATATE and similarly utilizes the somatostatin receptors to target the NET cells directly but utilizes the isotope lutetium-177, which causes DNA damage, destroying the cell over time.

Proper patient selection is primarily based on NET grade and stage, confirmation of high SSTR-expression based on functional imaging, progression of disease based on conventional imaging and/or clinical parameters, and renal function. PRRT is administered intravenously, usually over 4 cycles once every 2 months. Toxicity is quite low and primarily involves bone marrow suppression. Other potential toxicities include renal (reduced with co-administration of amino acids) and liver (which is typically transient but requires ongoing monitoring before, during, and after the therapy).