Identification
- Generic Name
- Dotatate gallium Ga-68
- DrugBank Accession Number
- DB13925
- Background
Dotatate gallium (Ga-68) is a somatostatin-2 receptor analog which is radiolabeled with gallium 68 as a positron-emitting radioisotope. Ga-68 dotatate has a high affinity for somatostatin-2 receptor and it is rapidly excreted from the nontarget sites which gives it an ideal candidate for imaging neuroendocrine tumors. Dotatate gallium (Ga-68) explotes its ability to detect somatostatin receptor scintigraphy and this characteristic tends to change with tumor grade which gives Ga-68 dotate a high diagnostic value.1 Dotatate gallium 68 was developed by Advanced Accelerator Applications USA, Inc. and FDA approved in June 1, 2016.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Dotatate gallium Ga-68 (DB13925)
- Weight
- Average: 1500.54
Monoisotopic: 1499.499317482 - Chemical Formula
- C65H87GaN14O19S2
- Synonyms
- (68Ga)Gallium dotatate
- 68Ga-DOTATATE
- 68Ga-DOTATOC
- DOTA-octreotate gallium Ga-68
- Dotatate gallium Ga-68
- Ga 68 DOTATOC
- Gallium (68Ga) DOTA-tate
- Gallium (68Ga) dotatate
- Gallium (Ga 68) dotatate
- Gallium 68 dotatate
- Gallium dotatate, Ga-68
- Gallium oxodotreotide Ga-68
- Gallium-DOTA-octreotate Ga-68
- Gallium-DOTA-octreotate, Ga-68
- Gatate
Pharmacology
- Indication
Dotatate gallium 68 is one of the most prominent radiopharmaceuticals used in imaging with positron emission tomography. It binds to the somatostatin-2 receptor which is usually overexpressed in many neuroendocrine tumors in both adult and pediatric patients.2 The neuroendocrine tumors are bening or malignant tumors produced in the hormone producing cells of the neuroendocrine system.7
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- Contraindications & Blackbox Warnings
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The overexpression of somatostatin receptor in tumor tissue has been widely studied and the usage of scintigraphy for the diagnostic of neuroendocrine tumors has been happening since the beggining of the 90s. The development of positron-emission tomography there has been an emerging and growing field for the discovery of tracer labeled somatostatin analogues like dotatate gallium 68.3 Even after all the reportes, the pharmacodynamic profile of dotatate gallium 68 has not been studied.
- Mechanism of action
The somatostatin receptor-based imaging is the preferred choice in the diagnostic and management of neuroendocrine tumors. The basis for the mechanism of dotatate gallium 68 is the binding of a ligand analog that is radiolabeled, in this case thye preferred binding site is the receptors of the subtype 2. The malignant cells are reported to overexpress the somatostatin subtype 2 receptor. Dotatate gallium 68 is a β+ emiting radionuclide with an emission yield that can be detected by the positron emission tomography and thus the seletive binding to the overexpressed somatostatin receptor will be detected.3
Target Actions Organism ASomatostatin receptor type 2 binderHumans - Absorption
Dotatate gallium 68 presents a higher affinity for the somatostatin receptor subtype 2 when compared with the other gallium 68 analogues. Intravenous administration of dotatate gallium 68 is absorbed and distributed to all the somatostatin subtype 2 receptor-containing organs like pituitary, thyroid, spleen, adrenals, kidney, pancreas, prostate, liver and salivary glands. There is no uptake in cerebral cortex or in the heart and the uptake presented in thymus and lung are very low.4
- Volume of distribution
The volume of distribution is registered in a range from 0.25-0.65 ml/cm3.6
- Protein binding
It presents binding to plasma proteins.5
- Metabolism
- Not Available
- Route of elimination
In the first four hours after the intravenous administration of dotatate gallium 68 there is an elimination of about 12% of the injected dose by the urine.4
- Half-life
The half-life of gallium 68 is estimated to be of 68 min.2
- Clearance
The pharmacokinetics of dotatate gallium 68 is matched to the short half-life of the isotope gallium 68 thus, this pharmaceutical presents a very fast blood clearance.2
- Adverse Effects
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Studies on dotatate gallium 68 have not been studied but the comparative studies to other non-radioactivity compounds showed no mutation.Label
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareLanreotide Lanreotide may decrease effectiveness of Dotatate gallium Ga-68 as a diagnostic agent. Octreotide Octreotide may decrease effectiveness of Dotatate gallium Ga-68 as a diagnostic agent. Pasireotide Pasireotide may decrease effectiveness of Dotatate gallium Ga-68 as a diagnostic agent. Somatostatin Somatostatin may decrease effectiveness of Dotatate gallium Ga-68 as a diagnostic agent. 
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- Not Available
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 9L17Y0H71P
- CAS number
- 1027785-90-5
- InChI Key
- XBJPSVQFCQFGDC-WSCOIBMGSA-K
- InChI
- InChI=1S/C65H90N14O19S2.Ga/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
- IUPAC Name
- (68Ga)gallium(3+) 2-[4-({[(1R)-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-yl)methyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentaazacycloicosan-19-yl]carbamoyl}-2-phenylethyl]carbamoyl}methyl)-7,10-bis(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetate
- SMILES
- [68Ga+3].C[C@@H](O)[C@H](NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](CC2=CC=CC=C2)NC(=O)CN2CCN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC([O-])=O)CC2)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@H](CC2=CNC3=C2C=CC=C3)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1)C(O)=O
References
- General References
- Kayani I, Bomanji JB, Groves A, Conway G, Gacinovic S, Win T, Dickson J, Caplin M, Ell PJ: Functional imaging of neuroendocrine tumors with combined PET/CT using 68Ga-DOTATATE (DOTA-DPhe1,Tyr3-octreotate) and 18F-FDG. Cancer. 2008 Jun;112(11):2447-55. doi: 10.1002/cncr.23469. [Article]
- Banerjee SR, Pomper MG: Clinical applications of Gallium-68. Appl Radiat Isot. 2013 Jun;76:2-13. doi: 10.1016/j.apradiso.2013.01.039. Epub 2013 Feb 20. [Article]
- Mojtahedi A, Thamake S, Tworowska I, Ranganathan D, Delpassand ES: The value of (68)Ga-DOTATATE PET/CT in diagnosis and management of neuroendocrine tumors compared to current FDA approved imaging modalities: a review of literature. Am J Nucl Med Mol Imaging. 2014 Aug 15;4(5):426-34. eCollection 2014. [Article]
- Shastry M, Kayani I, Wild D, Caplin M, Visvikis D, Gacinovic S, Reubi JC, Bomanji JB: Distribution pattern of 68Ga-DOTATATE in disease-free patients. Nucl Med Commun. 2010 Dec;31(12):1025-32. doi: 10.1097/MNM.0b013e32833f635e. [Article]
- Schottelius M, Simecek J, Hoffmann F, Willibald M, Schwaiger M, Wester HJ: Twins in spirit - episode I: comparative preclinical evaluation of [(68)Ga]DOTATATE and [(68)Ga]HA-DOTATATE. EJNMMI Res. 2015 Apr 10;5:22. doi: 10.1186/s13550-015-0099-x. eCollection 2015. [Article]
- Soto-Montenegro ML, Pena-Zalbidea S, Mateos-Perez JM, Oteo M, Romero E, Morcillo MA, Desco M: Meningiomas: a comparative study of 68Ga-DOTATOC, 68Ga-DOTANOC and 68Ga-DOTATATE for molecular imaging in mice. PLoS One. 2014 Nov 4;9(11):e111624. doi: 10.1371/journal.pone.0111624. eCollection 2014. [Article]
- FDA News and Events [Link]
- External Links
- FDA label
- Download (514 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Diagnostic Cardiac Sarcoidosis 1 3 Completed Diagnostic Neuroendocrine Tumors 1 3 Enrolling by Invitation Basic Science Neuroendocrine Tumors 1 3 Terminated Diagnostic Coronary Arteriosclerosis 1 2 Completed Diagnostic Carcinoid Tumors / Medulloblastomas / Neuroblastoma (NB) / Neuroendocrine Tumors 1 2 Completed Diagnostic Castration-Resistant Prostate Carcinoma / Metastatic Carcinoma of the Prostate / Stage IV Prostate Cancer AJCC v7 1 2 Completed Diagnostic Hypercalcemia / Hyperparathyroidism / Multiple Endocrine Neoplasia / Multiple Endocrine Neoplasia, Type 1 / Parathyroid Neoplasms 1 2 Not Yet Recruiting Diagnostic Infective Endocarditis (IE) 1 2 Recruiting Diagnostic ACTH / Cushing's Syndrome 1 2 Recruiting Diagnostic Neuroblastoma (NB) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9375498 No 2016-06-28 2032-08-10 US 
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility At pH above 7 can be soluble Long, N., Wong W. The Chemistry of Molecular Imaging. (2015) logP -3.69 Schottelius M., et al. EJNMMI Res. 2015; 5: 22. pKa 2.6 Long, N., Wong W. The Chemistry of Molecular Imaging. (2015) Radioactivity (mCi/mL) 5 'FDA label' - Predicted Properties
Property Value Source Water Solubility 0.068 mg/mL ALOGPS logP -0.99 ALOGPS logP -8.4 Chemaxon logS -4.4 ALOGPS pKa (Strongest Acidic) 0.47 Chemaxon pKa (Strongest Basic) 10.28 Chemaxon Physiological Charge -2 Chemaxon Hydrogen Acceptor Count 24 Chemaxon Hydrogen Donor Count 14 Chemaxon Polar Surface Area 505.95 Å2 Chemaxon Rotatable Bond Count 26 Chemaxon Refractivity 397.34 m3·mol-1 Chemaxon Polarizability 144.31 Å3 Chemaxon Number of Rings 6 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Binder
- General Function
- Somatostatin receptor activity
- Specific Function
- Receptor for somatostatin-14 and -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stimulates phosphotyrosine phosphatase and ...
- Gene Name
- SSTR2
- Uniprot ID
- P30874
- Uniprot Name
- Somatostatin receptor type 2
- Molecular Weight
- 41332.37 Da
References
- Banerjee SR, Pomper MG: Clinical applications of Gallium-68. Appl Radiat Isot. 2013 Jun;76:2-13. doi: 10.1016/j.apradiso.2013.01.039. Epub 2013 Feb 20. [Article]
Drug created at November 29, 2017 22:07 / Updated at October 06, 2020 17:43