Dotatate gallium Ga-68

Identification

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Name
Dotatate gallium Ga-68
Accession Number
DB13925
Type
Small Molecule
Groups
Approved, Investigational
Description

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.

Structure
Thumb
Synonyms
  • (68Ga)Gallium dotatate
  • 68Ga-DOTATATE
  • DOTA-octreotate gallium Ga-68
  • Dotatate gallium Ga-68
  • 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
Categories
UNII
9L17Y0H71P
CAS number
1027785-90-5
Weight
Average: 1502.33
Monoisotopic: 1500.496908
Chemical Formula
C65H87GaN14O19S2
InChI Key
XBJPSVQFCQFGDC-UZOALHFESA-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
IUPAC Name
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(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetate
SMILES
[Ga+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

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

Associated Conditions
Pharmacodynamics

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

TargetActionsOrganism
ASomatostatin receptor type 2
binder
Humans
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

Toxicity

Studies on dotatate gallium 68 have not been studied but the comparative studies to other non-radioactivity compounds showed no mutation.Label

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
LanreotideThe therapeutic efficacy of Dotatate gallium Ga-68 can be decreased when used in combination with Lanreotide.
OctreotideThe therapeutic efficacy of Dotatate gallium Ga-68 can be decreased when used in combination with Octreotide.
PasireotideThe therapeutic efficacy of Dotatate gallium Ga-68 can be decreased when used in combination with Pasireotide.
SomatostatinThe therapeutic efficacy of Dotatate gallium Ga-68 can be decreased when used in combination with Somatostatin.
VapreotideThe therapeutic efficacy of Dotatate gallium Ga-68 can be decreased when used in combination with Vapreotide.
Additional Data Available
  • Extended Description
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  • Severity
    Severity

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  • Evidence Level
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  • Action
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Food Interactions
Not Available

References

General References
  1. 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. [PubMed:18383518]
  2. 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. [PubMed:23522791]
  3. 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. [PubMed:25143861]
  4. 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. [PubMed:20926978]
  5. 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. [PubMed:25918675]
  6. 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. [PubMed:25369268]
  7. FDA News and Events [Link]
External Links
ChemSpider
23258514
FDA label
Download (514 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingDiagnosticMesenchymal Tumor / Oncogenic Osteomalacia1
1, 2CompletedDiagnosticNeuroendocrine Carcinomas1
2RecruitingDiagnosticCastration-Resistant Prostate Carcinoma / Metastatic Hormone Refractory Prostate Cancer / Stage IV Prostate Cancer AJCC v71

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US9375498No2016-06-282032-08-10Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityAt pH above 7 can be solubleLong, N., Wong W. The Chemistry of Molecular Imaging. (2015)
logP-3.69Schottelius M., et al. EJNMMI Res. 2015; 5: 22.
pKa2.6Long, N., Wong W. The Chemistry of Molecular Imaging. (2015)
Radioactivity (mCi/mL)5'FDA label'
Predicted Properties
PropertyValueSource
Water Solubility0.068 mg/mLALOGPS
logP-0.99ALOGPS
logP-8.7ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)1.32ChemAxon
pKa (Strongest Basic)10.29ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count24ChemAxon
Hydrogen Donor Count14ChemAxon
Polar Surface Area505.95 Å2ChemAxon
Rotatable Bond Count26ChemAxon
Refractivity397.34 m3·mol-1ChemAxon
Polarizability143.52 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

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
  1. 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. [PubMed:23522791]

Drug created on November 29, 2017 15:07 / Updated on May 01, 2019 11:54