Identification
NameFlorbetaben (18F)
Accession NumberDB09148
TypeSmall Molecule
GroupsApproved
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
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NeuraceqInjection, solution135 mCi/mLIntravenousPiramal Imaging, Sa2014-03-20Not applicableUs
NeuraceqInjection, solution300 MBq/mlIntravenousPiramal Imaging Limited2014-02-20Not applicableEu
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNIITLA7312TOI
CAS number902143-01-5
WeightAverage: 358.444
Monoisotopic: 358.192206368
Chemical FormulaC21H26FNO3
InChI KeyNCWZOASIUQVOFA-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.

TargetKindPharmacological actionActionsOrganismUniProt ID
Amyloid beta A4 proteinProteinyes
binder
HumanP05067 details
Related Articles
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 distributionNot 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

ClearanceNot 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 organismsNot Available
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions Not Available
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
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
ATC CodesV09AX06 — Florbetaben (18f)
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (3.7 MB)
MSDSNot Available
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
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, solutionIntravenous135 mCi/mL
Injection, solutionIntravenous300 MBq/ml
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7807135 No2009-03-182029-03-18Us
Properties
StateSolid
Experimental PropertiesNot 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 featuresNot Available
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassStilbenes
Sub ClassNot Available
Direct ParentStilbenes
Alternative ParentsStyrenes / Phenylalkylamines / Phenoxy compounds / Phenol ethers / Secondary alkylarylamines / Alkyl aryl ethers / Dialkyl ethers / Organofluorides / Hydrocarbon derivatives / Alkyl fluorides
SubstituentsStilbene / Phenoxy compound / Phenol ether / Phenylalkylamine / Styrene / Alkyl aryl ether / Secondary aliphatic/aromatic amine / Monocyclic benzene moiety / Benzenoid / Ether
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptorsaromatic 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 transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to ap...
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 for the epoxidation of endogenous cardiac arachidonic acid pools.
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 September 01, 2017 12:02