Technetium Tc-99m mebrofenin

Identification

Name
Technetium Tc-99m mebrofenin
Accession Number
DB09137
Type
Small Molecule
Groups
Approved
Description

Technetium Tc 99m Mebrofenin is a diagnostic radiopharmaceutical composed of diisopropyl-iminodiacetic acid (DISIDA) attached to a technetium-99m ion. Following intravenous injection, single photon emission computer tomography (SPECT) imaging of the liver or gallbladder is performed using a gamma camera to detect the gamma rays emitted by the technetium-99m as it decays. This is possible as Technetium-99m decays by isomeric transition to technetium-99 through the release of a gamma ray. Liver and gallbladder imaging is enabled through attachment to mebrofenin as this molecule has high hepatic uptake and fast biliary excretion, resulting in improved hepatic imaging. More specifically, mebrofenin is taken up into hepatocytes through the action of OATP1B1 and OATP1B3 transporters.

Currently available within a sterile kit, Tc-99m Mebrofenin is indicated for imaging of the liver and gallbladder.

Structure
Thumb
Synonyms
  • Bis(2-[[2-(3-bromo-2,4,6-trimethylanilino)-2-oxoethyl]-(carboxymethyl)amino]acetate) technetium
  • Technetium (99mTc) mebrofenin
  • Technetium Tc 99m diisopropyl-iminodiacetic acid
  • Technetium Tc 99m DISIDA
  • Technetium Tc 99m Mebrofenin
  • Technetium Tc-99m mebrofenin kit
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CholetecInjection, powder, lyophilized, for solution45 mg/1IntravenousBracco Diagnostics, Inc1987-01-21Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Kit for the Preparation of Technetium Tc 99m MebrofeninInjection, powder, lyophilized, for solution45 mg/10mLIntravenousPharmalucence, Inc.2008-01-29Not applicableUs
Unapproved/Other Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MebrofeninInjection, powder, lyophilized, for solution10 mg/1IntravenousAnazao Health Corporation2012-06-19Not applicableUs
Categories
UNII
7PV0B6ED98
CAS number
1415247-71-0
Weight
Average: 486.136
Monoisotopic: 484.953989
Chemical Formula
C15H19BrN2O5Tc
InChI Key
JLJSYHOPCNWUNE-NLQOEHMXSA-N
InChI
InChI=1S/C15H19BrN2O5.Tc/c1-8-4-9(2)15(10(3)14(8)16)17-11(19)5-18(6-12(20)21)7-13(22)23;/h4H,5-7H2,1-3H3,(H,17,19)(H,20,21)(H,22,23);/i;1+2
IUPAC Name
2-({[(3-bromo-2,4,6-trimethylphenyl)carbamoyl]methyl}(carboxymethyl)amino)acetic acid (⁹⁹Tc)technetium
SMILES
[99Tc].[H]OC(=O)C([H])([H])N(C([H])([H])C(=O)O[H])C([H])([H])C(=O)N([H])C1=C(C(Br)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H]

Pharmacology

Indication

Technetium Tc 99m Mebrofenin is indicated as a hepatobiliary imaging agent.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

Technetium Tc 99m Mebrofenin has no known pharmacologic activity at the recommended doses. It is used as a diagnostic agent as Technetium-99m decays by isomeric transition to technetium-99 through the release of a detectable gamma ray.

Absorption

Visualisation in the liver could be detected by 5 minutes and maximum liver uptake occurred at 11 minutes post-injection. Hepatic duct and gallbladder visualization occurred by 10 to 15 minutes and intestinal activity was visualized by 30 to 60 minutes in subjects with normal hepatobiliary function The mean percent injected dose remaining in the blood at 10 minutes was 17%.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination

The mean percent injected dose excreted in the urine during the first 3 hours was 1%.

Half life

Technetium Tc 99m decays by isomeric transition with a physical half-life of 6.02 hours.

Clearance

Following intravenous administration in normal subjects, Technetium Tc 99m Mebrofenin was rapidly cleared from the circulation.

Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
EltrombopagThe serum concentration of Technetium Tc-99m mebrofenin can be increased when it is combined with Eltrombopag.Approved
TeriflunomideThe serum concentration of Technetium Tc-99m mebrofenin can be increased when it is combined with Teriflunomide.Approved
Food Interactions
Not Available

References

General References
  1. Krishnamurthy GT, Turner FE: Pharmacokinetics and clinical application of technetium 99m-labeled hepatobiliary agents. Semin Nucl Med. 1990 Apr;20(2):130-49. [PubMed:2184521]
  2. de Graaf W, Hausler S, Heger M, van Ginhoven TM, van Cappellen G, Bennink RJ, Kullak-Ublick GA, Hesselmann R, van Gulik TM, Stieger B: Transporters involved in the hepatic uptake of (99m)Tc-mebrofenin and indocyanine green. J Hepatol. 2011 Apr;54(4):738-45. doi: 10.1016/j.jhep.2010.07.047. Epub 2010 Oct 1. [PubMed:21163547]
External Links
KEGG Drug
D06037
PubChem Compound
11431716
PubChem Substance
310265052
ChEMBL
CHEMBL2110555
Drugs.com
Drugs.com Drug Page
Wikipedia
Technetium_(99mTc)_mebrofenin
ATC Codes
V09DA04 — Technetium (99mtc) mebrofenin
FDA label
Download (2.51 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceNon-Alcoholic Steatohepatitis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous45 mg/1
Injection, powder, lyophilized, for solutionIntravenous45 mg/10mL
Injection, powder, lyophilized, for solutionIntravenous10 mg/1
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0568 mg/mLALOGPS
logP-0.39ALOGPS
logP0.45ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)2.81ChemAxon
pKa (Strongest Basic)2.13ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area106.94 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity89.27 m3·mol-1ChemAxon
Polarizability35 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Alpha amino acid amides
Alternative Parents
Alpha amino acids / Anilides / N-arylamides / Bromobenzenes / Dicarboxylic acids and derivatives / Aryl bromides / Trialkylamines / Secondary carboxylic acid amides / Amino acids / Carboxylic acids
show 4 more
Substituents
Alpha-amino acid amide / Alpha-amino acid / Anilide / N-arylamide / Bromobenzene / Halobenzene / Aryl bromide / Aryl halide / Monocyclic benzene moiety / Dicarboxylic acid or derivatives
show 18 more
Molecular Framework
Not Available
External Descriptors
Not Available

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. de Graaf W, Hausler S, Heger M, van Ginhoven TM, van Cappellen G, Bennink RJ, Kullak-Ublick GA, Hesselmann R, van Gulik TM, Stieger B: Transporters involved in the hepatic uptake of (99m)Tc-mebrofenin and indocyanine green. J Hepatol. 2011 Apr;54(4):738-45. doi: 10.1016/j.jhep.2010.07.047. Epub 2010 Oct 1. [PubMed:21163547]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. de Graaf W, Hausler S, Heger M, van Ginhoven TM, van Cappellen G, Bennink RJ, Kullak-Ublick GA, Hesselmann R, van Gulik TM, Stieger B: Transporters involved in the hepatic uptake of (99m)Tc-mebrofenin and indocyanine green. J Hepatol. 2011 Apr;54(4):738-45. doi: 10.1016/j.jhep.2010.07.047. Epub 2010 Oct 1. [PubMed:21163547]

Drug created on September 29, 2015 16:59 / Updated on November 09, 2017 04:46