Lutetium Lu 177 dotatate
DRACPC ID DRACPC0013
Active Ingredients Lutetium Lu 177 dotatate
Description A radioconjugate consisting of the tyrosine-containing somatostatin analog Tyr3-octreotate (TATE) conjugated with the bifunctional, macrocyclic chelating agent tetra-azacyclododecanetetra-acetic acid (DOTA) and radiolabeled with the beta-emitting radioisotope lutetium Lu 177, with potential imaging and antineoplastic activities. Lutetium Lu 177 dotatate belongs to an emerging form of treatments called Peptide Receptor Radionuclide Therapy (PRRT), which involves targeting tumours with molecules carrying radioactive particles that bind to specific receptors expressed by the tumour. Lutetium Lu 177 dotatate binds to somatostatin receptors (SSTRs), with high affinity to type 2 SSTR, present on the cell membranes of many types of neuroendocrine tumor (NET) cells. Upon binding and internalization, this radioconjugate specifically delivers a cytotoxic dose of beta radiation to SSTR-positive cells. Tyr3-octreotate (TATE) is an octreotide derivative in which phenylalanine at position 3 is substituted by tyrosine and position 8 threoninol is replaced with threonine. SSTRs have been shown to be present in large numbers on NET and their metastases, while most other normal tissues express low levels of SSTRs.
Synonyms 177Lu-DOTA-octreotate; 177Lu-dotatate; Dotatate lutenium Lu-177; Lu-DOTA-TATE; Lutetium dotatate Lu-177;; Lutetium Lu 177 dotatate
Type Small Molecule
Disease Gastroenteropancreatic neuroendocrine tumors (GEP-NETs)
Classification
Somatostatin and analogues Peptide and derivative Cyclic Peptide Receptor Radionuclide Therapy(PPRT) Cancer targeted Radioconjugates
Structure Information
Molecular Formula C65H87LuN14O19S2
Molecular Weight 1609.5
Active Sequence Not available
Sequence Length Not available
Modification Not available
IUPAC Name 2-[4-[2-[[(2R)-1-[[(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-4-[[(1S,2R)-1-carboxy-2-hydroxypropyl]carbamoyl]-7-[(1R)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicos-19-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoethyl]-7,10-bis(carboxylatomethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetate;lutetium-177(3+)
InChI InChI=1S/C65H90N14O19S2.Lu/c1-38(80)56-64(96)73-51(63(95)75-57(39(2)81)65(97)98)37-100-99-36-50(72-59(91)47(28-40-10-4-3-5-11-40)68-52(83)32-76-20-22-77(33-53(84)85)24-26-79(35-55(88)89)27-25-78(23-21-76)34-54(86)87)62(94)70-48(29-41-15-17-43(82)18-16-41)60(92)71-49(30-42-31-67-45-13-7-6-12-44(42)45)61(93)69-46(58(90)74-56)14-8-9-19-66;/h3-7,10-13,15-18,31,38-39,46-51,56-57,67,80-82H,8-9,14,19-30,32-37,66H2,1-2H3,(H,68,83)(H,69,93)(H,70,94)(H,71,92)(H,72,91)(H,73,96)(H,74,90)(H,75,95)(H,84,85)(H,86,87)(H,88,89)(H,97,98);/q;+3/p-3/t38-,39-,46+,47-,48+,49-,50+,51+,56+,57+;/m1./s1/i;1+2
InChI_Key MXDPZUIOZWKRAA-PRDSJKGBSA-K
SMILES C[C@H]([C@@H](C(O)=O)NC([C@@H]1CSSC[C@@H](C(N[C@H](C(N[C@@H](C(N[C@H](C(N[C@H](C(N1)=O)[C@H](O)C)=O)CCCCN)=O)CC2=CNC3=C2C=CC=C3)=O)CC4=CC=C(C=C4)O)=O)NC([C@H](NC(CN5CCN(CCN(CCN(CC5)CC([O-])=O)CC([O-])=O)CC([O-])=O)=O)CC6=CC=CC=C6)=O)=O)O.[177Lu+3]
External Codes
PubChem CID 76966897
DrugBank Accession Number DB13985
NCI Thesaurus Code C95020
UNII AE221IM3BB GSRS
CAS 437608-50-9
Drug approval
Drug indication
Indicated for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults.
| Drug Name | Strength | Dosage Form/Route | Company | Marketing Status | Drug ID | Approval year |
|---|---|---|---|---|---|---|
| Lutathera | 10mci/ml | Solution; Intravenous | Aaa Usa Inc | Prescription | NDA: 208700 | 2018 |
| Lutathera | unknown | Infusion; Intravenous | Advanced Accelerator Applications | Prescription | EMEA/H/C/004123 | 2017 |
| ClinicalTrials.gov Identifier | Title | Condition or disease | Phase | Purpose |
|---|---|---|---|---|
| NCT03972488 | A Phase III Multi-center, Randomized, Open-label Study to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NET | Gastro-enteropancreatic Neuroendocrine Tumor | Phase 3 | Treatment |
| NCT01456078 | A Multicenter Phase II-Study Evaluating Efficacy and Safety of 177Lu-DOTA-TATE Based on Kidney-Dosimetry in Patients With Disseminated Neuroendocrine Tumors | Neuroendocrine Tumors; Liver Metastases | Phase 2 | Treatment |
| NCT03325816 | Phase I/II Trial of Anti-PD-1 Checkpoint Inhibitor Nivolumab and 177Lu-DOTA0-Tyr3-Octreotate for Patients With Extensive-Stage Small Cell Lung Cancer | Small Cell Lung Cancer; Small Cell Lung Cancer Extensive Stage | Phase 1/2 | Treatment |
| NCT04750954 | A Phase 1b Trial of M3814 (Peposertib) in Combination With Lutetium 177 Dotatate for Well-Differentiated Somatostatin Receptor-Positive Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) | Neuroendocrine Neoplasm | Phase 1 | Treatment |
| NCT03971461 | A Single Arm, Open-label, Multicenter Phase II Study of 177Lu-DOTATATE Radionuclide in Adults With Progressive or High-risk Meningioma | Meningioma | Phase 2 | Treatment |
More clinical information is obtained from ClinicalTrials.gov.
