DOTA-TATE

DOTA-TATE (DOTATATE, DOTA-octreotate, oxodotreotide, DOTA-(Tyr3)-octreotate, and DOTA-0-Tyr3-Octreotate) is an amino acid peptide, with a covalently bonded DOTA bifunctional chelator. DOTA-TATE (DOTATATE, DOTA-octreotate, oxodotreotide, DOTA-(Tyr3)-octreotate, and DOTA-0-Tyr3-Octreotate) is an amino acid peptide, with a covalently bonded DOTA bifunctional chelator. DOTA-TATE can be bound with radionuclides such as gallium-68 and lutetium-177 to form radiopharmaceuticals for PET imaging or radionuclide therapy. 177Lu DOTA-TATE therapy is a form of peptide receptor radionuclide therapy (PRRT) which targets somatostatin receptors (SSR). In that form of application it is a form of targeted drug delivery. DOTA-TATE is a compound containing tyrosine3-octreotate, an SSR antagonist, and the bifunctional chelator DOTA (tetraxetan). SSRs are found with high density in numerous malignancies, including CNS, breast, lung, and lymphatics. The role of SSR antagonists (i.e. somatostatin and its analogs such as octreotide, somatuline and vapreotide) in neuroendocrine tumours (NETs) is well established, and massive SSR overexpression is present in several NETs. (Tyr3)-octreotate binds the transmembrane receptors of NETs with highest activity for SSR2 and is actively transported into the cell via endocytosis, allowing trapping of the radioactivity and increasing the probability of the desired double-strand DNA breakage (for tumour control). Trapping improves the probability of this kind of effect due to the relatively short range of the beta particles emitted by 177Lu, which have a maximum range in tissue of <2 mm. Bystander effects include cellular damage by free radical formation. 68Ga DOTA-TATE (GaTate) is used to measure tumor SSR density and wholebody bio-distribution via PET imaging. 68Ga DOTA-TATE imagery has a much higher sensitivity and resolution compared to 111In octreotide gamma camera or SPECT scans, due to intrinsic modality differences. 177Lu DOTA-TATE, trade name Lutathera, was approved by the FDA for the treatment of SSTR positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut and hindgut neuroendocrine tumors in adults, in January 2018. The recommended dosage is 4 cycles of 7.5 GBq every 8 weeks. About four to six hours after infusion, the exposure rate of the patient has fallen to less than 25 μSv/hour at one metre and the patients can be discharged from hospital. Alternatives to 177Lu-DOTATE include yttrium-90 DOTATATE or DOTATOC. The larger range of 90Y may make it more suitable for large tumors with 177Lu reserved for smaller volumes The European Commission approved marketing of Lutathera 'for the treatment of unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs) in adults' in October 2017.