Identification

Name
Florbetaben (18F)
Accession Number
DB09148
Type
Small Molecule
Groups
Approved
Description

Florbetaben is a fluorine-18 (18F)-labeled stilbene derivative used for Positron Emission Tomography (PET) imaging of the brain. It is indicated for the non-invasive detection of ß-amyloid neuritic plaque density in the brains of adult patients with cognitive impairment who are being evaluated for Alzheimer’s disease (AD) and other causes of cognitive impairment.

Structure
Thumb
Synonyms
  • Florbetaben F-18
External IDs
BAY-94-9172 / BAY-949172 / BAY94-9172 / ZK-6013443
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NeuraceqInjection, solution135 mCi/mLIntravenousPiramal Imaging, Sa2014-03-20Not applicableUs
NeuraceqInjection, solution300 MBq/mlIntravenousPiramal Imaging Limited2014-02-20Not applicableEu
Categories
UNII
TLA7312TOI
CAS number
902143-01-5
Weight
Average: 358.444
Monoisotopic: 358.192206368
Chemical Formula
C21H26FNO3
InChI Key
NCWZOASIUQVOFA-FWZJPQCDSA-N
InChI
InChI=1S/C21H26FNO3/c1-23-20-8-4-18(5-9-20)2-3-19-6-10-21(11-7-19)26-17-16-25-15-14-24-13-12-22/h2-11,23H,12-17H2,1H3/b3-2+/i22-1
IUPAC Name
4-[(E)-2-[4-(2-{2-[2-(¹⁸F)fluoroethoxy]ethoxy}ethoxy)phenyl]ethenyl]-N-methylaniline
SMILES
CNC1=CC=C(\C=C\C2=CC=C(OCCOCCOCC[18F])C=C2)C=C1

Pharmacology

Indication

Florbetaben is a radioactive diagnostic agent indicated for Positron Emission Tomography (PET) imaging of the brain to estimate β-amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer’s Disease (AD) and other causes of cognitive decline.

Structured Indications
Pharmacodynamics

Following intravenous administration, Neuraceq crosses the blood brain barrier and shows differential retention in brain regions that contain β-amyloid deposits. Differences in signal intensity between brain regions showing specific and non-specific Neuraceq uptake form the basis for the image interpretation method.

Mechanism of action

Florbetaben F18 is a F18-labeled stilbene derivative, which binds to β-amyloid plaques in the brain. The F 18 isotope produces a positron signal that is detected by a PET scanner.

TargetActionsOrganism
AAmyloid beta A4 protein
binder
Human
Absorption

Ten minutes after intravenous bolus injection of 300 MBq of Neuraceq in human volunteers, approximately 6% of the injected radioactivity was distributed to the brain. Florbetaben F 18 plasma concentrations declined by approximately 75% at 20 minutes post-injection, and by approximately 90% at 50 minutes.

Volume of distribution
Not Available
Protein binding

Florbetaben is 98.5% bound to plasma proteins.

Metabolism

In vitro studies show that metabolism of florbetaben is predominantly catalyzed by CYP2J2 and CYP4F2. Almost all F18 radioactivity in urine was excreted as polar metabolites of florbetaben F18 and only trace amounts of florbetaben F18 were detected.

Route of elimination

At 12 hours post-administration, approximately 30% of the injected radioactivity had been excreted in urine.

Half life

1 hr

Clearance
Not Available
Toxicity

The most commonly reported adverse reactions were: injection site reaction consisting of erythema (1.7 %), irritation (1.2 %), and pain (3.9 %).

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

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Syed YY, Deeks E: [(18)F]Florbetaben: a review in beta-amyloid PET imaging in cognitive impairment. CNS Drugs. 2015 Jul;29(7):605-13. doi: 10.1007/s40263-015-0258-7. [PubMed:26175116]
  2. Sabri O, Sabbagh MN, Seibyl J, Barthel H, Akatsu H, Ouchi Y, Senda K, Murayama S, Ishii K, Takao M, Beach TG, Rowe CC, Leverenz JB, Ghetti B, Ironside JW, Catafau AM, Stephens AW, Mueller A, Koglin N, Hoffmann A, Roth K, Reininger C, Schulz-Schaeffer WJ: Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer's disease: phase 3 study. Alzheimers Dement. 2015 Aug;11(8):964-74. doi: 10.1016/j.jalz.2015.02.004. Epub 2015 Mar 28. [PubMed:25824567]
  3. Zhang W, Oya S, Kung MP, Hou C, Maier DL, Kung HF: F-18 Polyethyleneglycol stilbenes as PET imaging agents targeting Abeta aggregates in the brain. Nucl Med Biol. 2005 Nov;32(8):799-809. [PubMed:16253804]
External Links
KEGG Drug
D10002
PubChem Compound
11501341
PubChem Substance
310265061
ChemSpider
9676143
ChEBI
79033
ChEMBL
CHEMBL566752
RxList
RxList Drug Page
Wikipedia
Florbetaben_(18F)
ATC Codes
V09AX06 — Florbetaben (18f)
FDA label
Download (3.7 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedDiagnosticAlzheimer's Disease (AD) / Amyloid Beta-Protein1
2CompletedDiagnosticAlzheimer's Disease (AD) / Amyloid Beta-Protein1
2CompletedDiagnosticAmyloid Beta-Protein / Down Syndrome (DS)1
2RecruitingDiagnosticAlzheimer's Disease (AD)1
3CompletedDiagnosticAlzheimer's Disease (AD)1
4CompletedHealth Services ResearchAlzheimer's Disease (AD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solutionIntravenous135 mCi/mL
Injection, solutionIntravenous300 MBq/ml
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7807135No2009-03-182029-03-18Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00103 mg/mLALOGPS
logP4.2ALOGPS
logP3.74ChemAxon
logS-5.5ALOGPS
pKa (Strongest Basic)4.62ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area39.72 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity104.86 m3·mol-1ChemAxon
Polarizability41.65 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
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 stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Stilbenes
Sub Class
Not Available
Direct Parent
Stilbenes
Alternative Parents
Styrenes / Phenylalkylamines / Phenoxy compounds / Phenol ethers / Aniline and substituted anilines / Secondary alkylarylamines / Alkyl aryl ethers / Dialkyl ethers / Organopnictogen compounds / Organofluorides
show 2 more
Substituents
Stilbene / Phenol ether / Styrene / Aniline or substituted anilines / Phenylalkylamine / Phenoxy compound / Secondary aliphatic/aromatic amine / Alkyl aryl ether / Monocyclic benzene moiety / Benzenoid
show 15 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
aromatic ether, substituted aniline, secondary amino compound, polyether, fluorine-18 radiopharmaceutical, stilbenoid (CHEBI:79033)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Binder
General Function
Transition metal ion binding
Specific Function
Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and tra...
Gene Name
APP
Uniprot ID
P05067
Uniprot Name
Amyloid beta A4 protein
Molecular Weight
86942.715 Da

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
This enzyme metabolizes arachidonic acid predominantly via a NADPH-dependent olefin epoxidation to all four regioisomeric cis-epoxyeicosatrienoic acids. One of the predominant enzymes responsible f...
Gene Name
CYP2J2
Uniprot ID
P51589
Uniprot Name
Cytochrome P450 2J2
Molecular Weight
57610.165 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Not Available
Specific Function
Not Available
Gene Name
CYP4F2
Uniprot ID
P78329
Uniprot Name
Phylloquinone omega-hydroxylase CYP4F2
Molecular Weight
59852.825 Da

Drug created on October 01, 2015 11:06 / Updated on November 09, 2017 04:46