Lutetium-177 dotatate, also known as Lu-177 oxodotreotide and by the trade name Lutathera (Novartis Pharmaceuticals Corporation, USA), is a theranostic agent approved as a second-line agent for the treatment of patients with inoperable and/or metastatic well-differentiated neuroendocrine tumors involving the pancreas or gastrointestinal tract (GEP-NETs). The treatment works by utilizing DOTA-TATE, a molecule with affinity for the somatostatin receptor SSTR2, fused to the radioactive molecule Lutetium-177, which kills tumor cells.
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Characteristics
Lu-177 half-life of 160 hours (6.65 days)
beta minus decay
beta particle maximum penetration of 2.2 mm allows for targeted cytotoxic effects with limited effect on surrounding normal tissue
gamma emission with photopeak of 208 keV used for imaging
Use
Before treatment, a diagnostic PET is performed using Gallium-68 dotatate to determine sites of disease and ensure target receptor affinity. Less commonly, In-111 DTPA octreotide or In-111 pentetreotide (Octreoscan) can also be used.
Lutetium-177 DOTATATE is administered in four intravenous doses of 200 mCi (7.4 GBq) at eight-week intervals. The dose and timing may be modified if the patient had a prior adverse reaction as determined by their physician.
Lutetium-177 DOTATATE is primarily eliminated through renal excretion. Co-administration with the amino acids lysine and arginine reduces renal toxicity. Anti-emetics are also given to prevent nausea, a common side-effect.
Potential side effects
myelosuppression: anemia, neutropenia, and thrombocytopenia
nausea, vomiting, and fatigue
rare: liver damage; more common in patients with hepatic tumor burden
carcinoid crisis may result from release of hormones from dying cancer cells.
Lutetium-177 dotatate is not approved for use in pregnant and breastfeeding patients.
History and etymology
The standard of care treatment for inoperable well-differentiated neuroendocrine tumors is a long-acting somatostatin analog such as octreotide. The multicentric NETTER-1 trial phase III study initially demonstrated significantly longer progression-free survival in a population of 229 patients when comparing treatment with Lu-177 DOTATATE plus standard of care versus standard of care alone. However, no statistically significant overall survival (48 months versus 36.3 months) was found. This difference of 11.7 months can still be clinically relevant.
Lu-177 DOTATATE was approved for medical use in adults with inoperable or metastatic GEP-NETs by the European Medicines Agency in 2017 and by the FDA in 2018.
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