Gallium citrate Ga-67

Identification

Name
Gallium citrate Ga-67
Accession Number
DB06784
Description

Gallium citrate Ga 67 is the citrate salt of the radioisotope gallium Ga 67. Although the mechanism is unknown, gallium Ga 67 concentrates in lysosomes and is bound to a soluble intracellular protein in certain viable primary and metastatic tumors and focal sites of inflammation, allowing scintigraphic localization. Ga-67 scintigraphy (GS) cannot differentiate between tumor and acute inflammation. [NCI Thesaurus]

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 256.0279
Monoisotopic: 255.931732429
Chemical Formula
C6H5GaO7
Synonyms
  • Gallium (67 Ga) citrate
  • Gallium citrate Ga 67
  • Gallium citrate Ga-67
  • Gallium-67 Citrate

Pharmacology

Indication

Gallium Citrate Ga 67 Injection may be useful to demonstrate the presence and extent of Hodgkin's disease, lymphoma, and bronchogenic carcinoma. Positive gallium Ga-67 uptake in the absence of prior symptoms warrants follow-up as an indication of a potential disease state. Gallium Citrate Ga 67 Injection may be useful as an aid in detecting some acute inflammatory lesions.

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

It has been reported in the scientific literature that following intravenous injection, the highest tissue concentration of gallium Ga-67 - other than tumors and sites of infection - is the renal cortex. After the first day, the maximum concentration shifts to bone and lymph nodes and after the first week, to liver and spleen. Gallium Ga-67 is excreted relatively slowly from the body. The average whole body retention is 65 percent after seven days, with 26 percent having been excreted in the urine and 9 percent in the stools.

Mechanism of action

Gallium Citrate Ga 67, with no carrier added, has been found to concentrate in certain viable primary and metastatic tumors as well as focal sites of infection. The body generally handles Ga3+ as though it were ferric iron (Fe-III), and thus the free isotope ion is bound (and concentrates) in areas of inflammation, such as an infection site, and also areas of rapid cell division. Ga-67 binds to transferrin, leukocyte lactoferrin, bacterial siderophores, inflammatory proteins, and cell-membranes in neutrophils, both living and dead. Lactoferrin is contained within leukocytes. Ga-67 may bind to lactoferrin and be transported to sites of inflammation, or binds to lactoferrin released during bacterial phagocytosis at infection sites (and remains due to binding with macrophage receptors). Ga-67 also attaches to the siderophore molecules of bacteria themselves, and for this reason can be used in leukopenic patients with bacterial infection (here it attaches directly to bacterial proteins, and leukocytes are not needed). Uptake is thought to be associated with a range of tumour properties including transferring receptors, anaerobic tumor metabolism and tumor perfusion and vascular permeability.

Absorption

The body generally handles Ga3+ as though it were ferric iron (Fe-III). However, gallium can not be reduced in vivo. Therefore, ferric ion is easily reduced and interacts with protoporphyrin IX to form heme, gallium remains bound to iron-transport proteins and carrier molecules.

Volume of distribution
Not Available
Protein binding

Gallium binds to at least four iron-binding molecules: transferrin, lactoferrin, ferritin, and siderophores. Siderophores are compounds of low molecular weight that facilitate iron uptake by microorganisms.

Metabolism
Not Available
Route of elimination

No urinary excretion; elimination primarily via fecal excretion.

Half-life

78.26 hours

Clearance
Not Available
Adverse Effects
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Toxicity
Not Available
Affected organisms
  • Humans and other mammals
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.
Not Available
Food Interactions
No interactions found.

Products

Active Moieties
NameKindUNIICASInChI Key
Gallium cation Ga-67ionic99T03J52W0Not AvailableCKHJYUSOUQDYEN-OIOBTWANSA-N
International/Other Brands
Neoscan (Medi-Physics, Inc.)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
GalliumInjection2.0 mCi/1mLIntravenousLantheus Medical Imaging1976-05-17Not applicableUs
Gallium Citrate Ga-67Injection, solution2 mCi/1mLIntravenousMallinckrodt2008-02-212017-07-01Us
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as tricarboxylic acids and derivatives. These are carboxylic acids containing exactly three carboxyl groups.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Tricarboxylic acids and derivatives
Direct Parent
Tricarboxylic acids and derivatives
Alternative Parents
Tertiary alcohols / Carboxylic acid salts / Carboxylic acids / Organic salts / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Alcohol / Aliphatic acyclic compound / Carbonyl group / Carboxylic acid / Carboxylic acid salt / Hydrocarbon derivative / Organic oxide / Organic oxygen compound / Organic salt / Organooxygen compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
Not Available

Chemical Identifiers

UNII
4LJK511Z86
CAS number
41183-64-6
InChI Key
YEEGWNXDUZONAA-RYDPDVNUSA-K
InChI
InChI=1S/C6H8O7.Ga/c7-3(8)1-6(13,5(11)12)2-4(9)10;/h13H,1-2H2,(H,7,8)(H,9,10)(H,11,12);/q;+3/p-3/i;1-3
IUPAC Name
(⁶⁷Ga)gallium(3+) ion 2-hydroxypropane-1,2,3-tricarboxylate
SMILES
[67Ga+3].OC(CC([O-])=O)(CC([O-])=O)C([O-])=O

References

General References
  1. Hoffer P: Gallium: mechanisms. J Nucl Med. 1980 Mar;21(3):282-5. [PubMed:6988551]
  2. Gallium-Mechanism article [Link]
  3. Gallium citrate [Link]
  4. Drugs.com [Link]
  5. FDA Approved Drug Products: Gallium Citrate Ga 67 Intravenous Injection [Link]
PubChem Compound
65430
PubChem Substance
347827795
ChemSpider
58893
RxNav
272758
ChEBI
31645
ChEMBL
CHEMBL1200994
Drugs.com
Drugs.com Drug Page

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1TerminatedTreatmentNeoplasms, Brain / Tumors of the Central Nervous System1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Bristol-Myers Squibb Co.
  • Mallinckrodt Inc.
Dosage Forms
FormRouteStrength
InjectionIntravenous74 MBq
InjectionIntravenous2.0 mCi/1mL
Injection, solutionIntravenous2 mCi/1mL
Injection, solutionIntravenous74 MBq/mL
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility3.21 mg/mLALOGPS
logP1.06ALOGPS
logP-1.3ChemAxon
logS-2.1ALOGPS
pKa (Strongest Acidic)3.05ChemAxon
pKa (Strongest Basic)-4.2ChemAxon
Physiological Charge-3ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area140.62 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity68.14 m3·mol-1ChemAxon
Polarizability14.25 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption-0.7684
Blood Brain Barrier+0.9683
Caco-2 permeable-0.6826
P-glycoprotein substrateNon-substrate0.7725
P-glycoprotein inhibitor INon-inhibitor0.953
P-glycoprotein inhibitor IINon-inhibitor0.9204
Renal organic cation transporterNon-inhibitor0.9563
CYP450 2C9 substrateNon-substrate0.8503
CYP450 2D6 substrateNon-substrate0.8955
CYP450 3A4 substrateNon-substrate0.7068
CYP450 1A2 substrateNon-inhibitor0.9115
CYP450 2C9 inhibitorNon-inhibitor0.9313
CYP450 2D6 inhibitorNon-inhibitor0.9365
CYP450 2C19 inhibitorNon-inhibitor0.9252
CYP450 3A4 inhibitorNon-inhibitor0.9071
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9909
Ames testNon AMES toxic0.8123
CarcinogenicityNon-carcinogens0.622
BiodegradationReady biodegradable0.8965
Rat acute toxicity1.8998 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9909
hERG inhibition (predictor II)Non-inhibitor0.9791
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available

Transporters

Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Substrate
General Function
Virus receptor activity
Specific Function
Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes. Endosomal acidification leads to iron release. The apotransferri...

Components:
References
  1. Hoffer P: Gallium: mechanisms. J Nucl Med. 1980 Mar;21(3):282-5. [PubMed:6988551]
  2. Chitambar CR, Narasimhan J: Targeting iron-dependent DNA synthesis with gallium and transferrin-gallium. Pathobiology. 1991;59(1):3-10. doi: 10.1159/000163609. [PubMed:1645976]
  3. Gallium-Mechanism article [Link]
Kind
Protein
Organism
Bos taurus
Pharmacological action
Yes
Actions
Substrate
General Function
Not Available
Specific Function
Not Available
Gene Name
Not Available
Uniprot ID
Q19KS1
Uniprot Name
Lactoferrin
Molecular Weight
39208.975 Da
References
  1. Hoffer P: Gallium: mechanisms. J Nucl Med. 1980 Mar;21(3):282-5. [PubMed:6988551]
  2. Gallium-Mechanism article [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Substrate
General Function
Iron ion binding
Specific Function
Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. Also plays a ro...
Gene Name
FTL
Uniprot ID
P02792
Uniprot Name
Ferritin light chain
Molecular Weight
20019.49 Da
References
  1. Hoffer P: Gallium: mechanisms. J Nucl Med. 1980 Mar;21(3):282-5. [PubMed:6988551]
  2. Gallium-Mechanism article [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Substrate
General Function
Iron ion binding
Specific Function
Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity. Iron is taken up in the ferrous form and deposited as ferric hydroxides after ...
Gene Name
FTH1
Uniprot ID
P02794
Uniprot Name
Ferritin heavy chain
Molecular Weight
21225.47 Da
References
  1. Hoffer P: Gallium: mechanisms. J Nucl Med. 1980 Mar;21(3):282-5. [PubMed:6988551]
  2. Gallium-Mechanism article [Link]

Drug created on September 14, 2010 10:21 / Updated on June 12, 2020 11:42

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