Edotreotide gallium Ga-68

Identification

Summary

Edotreotide gallium Ga-68 is a radioactive diagnostic agent used in PET scans for somatostatin receptor positive neuroendocrine tumors in adult and pediatric patients.

Generic Name
Edotreotide gallium Ga-68
DrugBank Accession Number
DB15494
Background

Edotreotide gallium Ga-68 is an 8 amino acid peptide bound to the chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA).8 Edotreotide gallium Ga-68 is indicated for localizing somatostatin receptor positive neuroendocrine tumors by positron emission tomography.7 Dotatate gallium Ga-68 is used for a similar indication.2 Dotatate gallium Ga-68 has lower tumor uptake but this data is highly variable between patients.2

Edotreotide gallium Ga-68 was granted FDA approval on 21 August 2019.7

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 1486.55
Monoisotopic: 1485.520052927
Chemical Formula
C65H89GaN14O18S2
Synonyms
  • Edotreotide Gallium Ga-68
  • Gallium (68Ga) edotreotide
  • Gallium edotreotide Ga-68
  • Gallium Ga 68-dotatoc
  • Gallium Ga 68-edotreotide
  • Gallium Ga-68 edotreotide

Pharmacology

Indication

Edotreotide gallium Ga-68 is a radioactive diagnostic compound used in positron emission tomography (PET) for diagnose somatostatin receptor positive neuroendocrine tumors in pediatrics and adults.7

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Edotreotide gallium Ga-68 binds to somatostatin receptors where it emits beta particle radiation for detection by positron emission tomography.7 The duration of action is short as it has short radioactive and biological half lives.4,8 Patients should hydrate before and after the administration of this medication to encourage frequent urination and rapid clearance.7

Mechanism of action

Edotreotide gallium Ga-68 binds to somatostatin receptors, with higher affinity for somatostatin receptor type 2, where it emits beta particle radiation for detection by positron emission tomography (PET).7

TargetActionsOrganism
ASomatostatin receptor type 2
ligand
Humans
ASomatostatin receptor type 5
ligand
Humans
ASomatostatin receptor type 3
ligand
Humans
ASomatostatin receptor type 1
ligand
Humans
Absorption

Edotreotide gallium Ga-68 reaches 80% activity in tumors within 30 minutes,4 and reaches its highest activity in tumors 70±20min post injection.8 Edotreotide is mostly taken up into the spleen, followed by kidneys, liver, pituitary, thyroid, and adrenal gland.3,4,8 Accumulation in non-tumor tissue reaches a maximum within 40 minutes.4

Volume of distribution

Data regarding the volume of distribution of this medication is not readily available.7

Protein binding

Data suggests edotreotide gallium-Ga 68 may bind to proteins in serum.6 The extent of serum protein binding and which proteins it binds to are not described in the literature.

Metabolism

Edotreotide gallium Ga-68 is largely unmetabolized.8 4 hours post injection there are no metabolites or degradation products detectable in serum.4

Route of elimination

16% of a Edotreotide gallium Ga-68 dose is eliminated in the urine within 2h.1,7 It is expected that Edotreotide gallium Ga-68 is exclusively eliminated in the urine.1,7 In animal studies, edotreotide Y-90 was >80% eliminated in the urine within 24h, with 95.6±3.4% being unmetabolized.3,8 <1% of a dose is detected in the feces.5

Half-life

Edotreotide gallium Ga-68 has a radioactive half life of 68 minutes.4,8 Edotreotide gallium Ga-68 has two half lives, 2.0±0.3min and 48±7min for its removal from blood.4,8

Clearance

Data regarding the clearance of this medication is not readily available.7

Adverse Effects
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Toxicity

The LD50 of this medication is not readily available.7

In the event of an overdose, give patients plenty of fluids and diuretics if necessary to encourage frequent urination.7 If possible, an estimation of radioactive dose should be performed.7

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.
DrugInteraction
LanreotideLanreotide may decrease effectiveness of Edotreotide gallium Ga-68 as a diagnostic agent.
OctreotideOctreotide may decrease effectiveness of Edotreotide gallium Ga-68 as a diagnostic agent.
PasireotidePasireotide may decrease effectiveness of Edotreotide gallium Ga-68 as a diagnostic agent.
SomatostatinSomatostatin may decrease effectiveness of Edotreotide gallium Ga-68 as a diagnostic agent.
Interactions
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Food Interactions
No interactions found.

Products

Products
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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Ga-68-DOTATOCInjection, solution4 mCi/1mLIntravenousUIHC – P E T Imaging Center2019-09-01Not applicableUS flag
Somakit TocKitIntravenousAdvanced Accelerator Applications2020-12-22Not applicableEU flag

Categories

ATC Codes
V09IX09 — Gallium (68ga) edotreotide
Drug Categories
Classification
Not classified
Affected organisms
Not Available

Chemical Identifiers

UNII
Y68179SY2L
CAS number
2101630-92-4
InChI Key
PZBPHYLKIMOZPR-FIYGWYQWSA-K
InChI
InChI=1S/C65H92N14O18S2.Ga/c1-39(81)51(36-80)72-64(96)53-38-99-98-37-52(73-60(92)48(28-41-10-4-3-5-11-41)68-54(84)32-76-20-22-77(33-55(85)86)24-26-79(35-57(89)90)27-25-78(23-21-76)34-56(87)88)63(95)70-49(29-42-15-17-44(83)18-16-42)61(93)71-50(30-43-31-67-46-13-7-6-12-45(43)46)62(94)69-47(14-8-9-19-66)59(91)75-58(40(2)82)65(97)74-53;/h3-7,10-13,15-18,31,39-40,47-53,58,67,80-83H,8-9,14,19-30,32-38,66H2,1-2H3,(H,68,84)(H,69,94)(H,70,95)(H,71,93)(H,72,96)(H,73,92)(H,74,97)(H,75,91)(H,85,86)(H,87,88)(H,89,90);/q;+3/p-3/t39-,40-,47+,48-,49+,50-,51-,52+,53+,58+;/m1./s1/i;1-2
IUPAC Name
(68Ga)gallium(3+) 2-[4-({[(1R)-1-{[(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-4-{[(2R,3R)-1,3-dihydroxybutan-2-yl]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](CO)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

References

General References
  1. Hartmann H, Zophel K, Freudenberg R, Oehme L, Andreeff M, Wunderlich G, Eisenhofer G, Kotzerke J: [Radiation exposure of patients during 68Ga-DOTATOC PET/CT examinations]. Nuklearmedizin. 2009;48(5):201-7. doi: 10.3413/nukmed-0214. Epub 2009 Jul 28. [PubMed:19639164]
  2. Poeppel TD, Binse I, Petersenn S, Lahner H, Schott M, Antoch G, Brandau W, Bockisch A, Boy C: 68Ga-DOTATOC versus 68Ga-DOTATATE PET/CT in functional imaging of neuroendocrine tumors. J Nucl Med. 2011 Dec;52(12):1864-70. doi: 10.2967/jnumed.111.091165. Epub 2011 Nov 9. [PubMed:22072704]
  3. de Jong M, Bakker WH, Krenning EP, Breeman WA, van der Pluijm ME, Bernard BF, Visser TJ, Jermann E, Behe M, Powell P, Macke HR: Yttrium-90 and indium-111 labelling, receptor binding and biodistribution of [DOTA0,d-Phe1,Tyr3]octreotide, a promising somatostatin analogue for radionuclide therapy. Eur J Nucl Med. 1997 Apr;24(4):368-71. doi: 10.1007/bf00881807. [PubMed:9096086]
  4. Hofmann M, Maecke H, Borner R, Weckesser E, Schoffski P, Oei L, Schumacher J, Henze M, Heppeler A, Meyer J, Knapp H: Biokinetics and imaging with the somatostatin receptor PET radioligand (68)Ga-DOTATOC: preliminary data. Eur J Nucl Med. 2001 Dec;28(12):1751-7. doi: 10.1007/s002590100639. Epub 2001 Oct 31. [PubMed:11734911]
  5. Kwekkeboom DJ, Kooij PP, Bakker WH, Macke HR, Krenning EP: Comparison of 111In-DOTA-Tyr3-octreotide and 111In-DTPA-octreotide in the same patients: biodistribution, kinetics, organ and tumor uptake. J Nucl Med. 1999 May;40(5):762-7. [PubMed:10319747]
  6. Bangard M, Behe M, Guhlke S, Otte R, Bender H, Maecke HR, Biersack HJ: Detection of somatostatin receptor-positive tumours using the new 99mTc-tricine-HYNIC-D-Phe1-Tyr3-octreotide: first results in patients and comparison with 111In-DTPA-D-Phe1-octreotide. Eur J Nucl Med. 2000 Jun;27(6):628-37. doi: 10.1007/s002590050556. [PubMed:10901448]
  7. FDA Approved Drug Products: Gallium Dotatoc GA 68 [Link]
  8. EMA Assessment Report: SomaKit TOC [Link]
ChemSpider
52083916
RxNav
2199391

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2RecruitingDiagnosticMeningiomas1
1, 2TerminatedDiagnosticCarcinoid Tumors / Neuroblastomas / Neuroendocrine Tumors / Paraganglioma1
0TerminatedDiagnosticMeningiomas / Metastatic Well Differentiated Neuroendocrine Neoplasm / Multiple Endocrine Neoplasia Type 1 / Neuroendocrine Neoplasms / Somatostatin Positive Neoplastic Cells Present / Von Hippel-Lindau Syndrome1
Not AvailableNot Yet RecruitingDiagnosticMyocarditis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solutionIntravenous4 mCi/1mL
Injection, solutionParenteral
Injection, powder, lyophilized, for solutionIntravenous
KitIntravenous
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0646 mg/mLALOGPS
logP1.66ALOGPS
logP-9.6ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)-0.48ChemAxon
pKa (Strongest Basic)10.28ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count23ChemAxon
Hydrogen Donor Count14ChemAxon
Polar Surface Area488.88 Å2ChemAxon
Rotatable Bond Count26ChemAxon
Refractivity397.48 m3·mol-1ChemAxon
Polarizability143.64 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

Targets

Drugtargets
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Ligand
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. FDA Approved Drug Products: Gallium Dotatoc GA 68 [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Ligand
General Function
Somatostatin receptor activity
Specific Function
Receptor for somatostatin 28 and to a lesser extent for somatostatin-14. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase. Increases cell growth inhibition act...
Gene Name
SSTR5
Uniprot ID
P35346
Uniprot Name
Somatostatin receptor type 5
Molecular Weight
39201.925 Da
References
  1. EMA Assessment Report: SomaKit TOC [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Ligand
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.
Gene Name
SSTR3
Uniprot ID
P32745
Uniprot Name
Somatostatin receptor type 3
Molecular Weight
45846.995 Da
References
  1. EMA Assessment Report: SomaKit TOC [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Ligand
General Function
Somatostatin receptor activity
Specific Function
Receptor for somatostatin with higher affinity for somatostatin-14 than -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stim...
Gene Name
SSTR1
Uniprot ID
P30872
Uniprot Name
Somatostatin receptor type 1
Molecular Weight
42685.77 Da
References
  1. EMA Assessment Report: SomaKit TOC [Link]

Drug created on September 17, 2019 20:38 / Updated on March 04, 2021 09:26