Identification

Name
Flutemetamol (18F)
Accession Number
DB09151
Type
Small Molecule
Groups
Approved
Description

Flutemetamol (18F) is a PET scanning radiopharmaceutical containing the radionuclide fluorine-18. It is 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) or other causes of cognitive decline.

Structure
Thumb
Synonyms
  • 2-[3-(18F)fluoro-4-(methylamino)phenyl]-1,3-benzothiazol-6-ol
  • [18F]-Flutemetamol
  • flutemetamol (18F)
  • Flutemetamol F 18
  • Flutemetamol F-18
  • Flutemetamol F18
External IDs
(18F)AH110690
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
VizamylSolution4.05 mCi/mLIntravenousMedi Physics Inc.2014-01-01Not applicableUs
Categories
UNII
L49M066S0O
CAS number
765922-62-1
Weight
Average: 273.32
Monoisotopic: 273.060146823
Chemical Formula
C14H11FN2OS
InChI Key
VVECGOCJFKTUAX-HUYCHCPVSA-N
InChI
InChI=1S/C14H11FN2OS/c1-16-11-4-2-8(6-10(11)15)14-17-12-5-3-9(18)7-13(12)19-14/h2-7,16,18H,1H3/i15-1
IUPAC Name
2-[3-(¹⁸F)fluoro-4-(methylamino)phenyl]-1,3-benzothiazol-6-ol
SMILES
CNC1=C([18F])C=C(C=C1)C1=NC2=CC=C(O)C=C2S1

Pharmacology

Indication

Flutemetamol F18 is 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) or other causes of cognitive decline.

Structured Indications
Pharmacodynamics

Following intravenous injection, flutemetamol F 18 diffuses across the human blood-brain barrier and produces a radioactivity signal detectable throughout the brain. Subsequently, cerebral perfusion decreases the brain flutemetamol F 18 content, with differential retention of the drug in cortical areas that contain β-amyloid aggregates compared to areas that lack the aggregates.

Mechanism of action

Fluorine-18 (F 18) is a cyclotron-produced radionuclide that decays by positron emission (β+ decay, 96.7%) and orbital electron capture (3.3%) to stable oxygen-18 with a physical half-life of 109.8 minutes. The positron can undergo annihilation with an electron to produce two gamma rays; the energy of each gamma ray is 511 keV. After flumetamol F18 is given intravenously, it accumulates in beta amyloid plaques in the brain, and thus becomes visible via positron emission tomography (PET).

TargetActionsOrganism
AAmyloid beta A4 protein
binder
Human
Absorption

The time-activity curves for flutemetamol F 18 in the brain of subjects with positive scans shows continual signal increases from time zero through 30 minutes post administration, with stable values thereafter up to at least 120 minutes post-injection. Following intravenous injection of 185 MBq (5 mCi) of Vizamyl in humans, flutemetamol F 18 plasma concentrations declined by approximately 75% in the first 20 minutes post-injection, and by approximately 90% in the first 180 minutes.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

The F 18 in circulation during the 30-120 minutes imaging window in plasma was principally associated with flutemetamol metabolites.

Route of elimination

Excretion was found to be approximately 37% renal and 52% hepatobiliary.

Half life
Not Available
Clearance
Not Available
Toxicity

Most commonly reported adverse reactions were flushing (2%), headache (1%), increased blood pressure (2%), nausea (1%), and dizziness (1%).

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. Beach TG, Thal DR, Zanette M, Smith A, Buckley C: Detection of Striatal Amyloid Plaques with [18F]flutemetamol: Validation with Postmortem Histopathology. J Alzheimers Dis. 2016 Mar 31;52(3):863-73. doi: 10.3233/JAD-150732. [PubMed:27031469]
  2. Heurling K, Leuzy A, Zimmer ER, Lubberink M, Nordberg A: Imaging beta-amyloid using [(18)F]flutemetamol positron emission tomography: from dosimetry to clinical diagnosis. Eur J Nucl Med Mol Imaging. 2016 Feb;43(2):362-73. doi: 10.1007/s00259-015-3208-1. Epub 2015 Oct 6. [PubMed:26440450]
External Links
KEGG Drug
D10231
PubChem Compound
15950376
PubChem Substance
310265064
ChemSpider
13092196
ChEBI
76611
ChEMBL
CHEMBL2042122
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Flutemetamol_(18F)
ATC Codes
V09AX04 — Flutemetamol (18f)
FDA label
Download (4.64 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1RecruitingBasic ScienceAlzheimer's Disease (AD)1
2CompletedBasic ScienceAlzheimer's Disease (AD)1
3RecruitingDiagnosticAlzheimer's Disease (AD) and Related Disorders1
Not AvailableRecruitingNot AvailableAlzheimer's Disease (AD) / Dementias / Mild Cognitive Impairment (MCI)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionIntravenous4.05 mCi/mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7351401No2003-01-242023-01-24Us
US8691185No2003-01-242023-01-24Us
US7270800No2007-04-142027-04-14Us
US8236282No2004-05-212024-05-21Us
US8916131No2008-09-162028-09-16Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0135 mg/mLALOGPS
logP4.16ALOGPS
logP3.45ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)9.23ChemAxon
pKa (Strongest Basic)2.89ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area45.15 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity84.62 m3·mol-1ChemAxon
Polarizability28.19 Å3ChemAxon
Number of Rings3ChemAxon
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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 benzothiazoles. These are organic compounds containing a benzene fused to a thiazole ring (a five-membered ring with four carbon atoms, one nitrogen atom and one sulfur atom).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzothiazoles
Sub Class
Not Available
Direct Parent
Benzothiazoles
Alternative Parents
Phenylalkylamines / Aniline and substituted anilines / Secondary alkylarylamines / Fluorobenzenes / 1-hydroxy-2-unsubstituted benzenoids / Aryl fluorides / Thiazoles / Heteroaromatic compounds / Azacyclic compounds / Organopnictogen compounds
show 3 more
Substituents
1,3-benzothiazole / Aniline or substituted anilines / Phenylalkylamine / Fluorobenzene / Halobenzene / Secondary aliphatic/aromatic amine / 1-hydroxy-2-unsubstituted benzenoid / Monocyclic benzene moiety / Aryl halide / Benzenoid
show 16 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
benzothiazoles, secondary amino compound, aromatic amine, ring assembly, fluorine-18 radiopharmaceutical (CHEBI:76611)

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
References
  1. Beach TG, Thal DR, Zanette M, Smith A, Buckley C: Detection of Striatal Amyloid Plaques with [18F]flutemetamol: Validation with Postmortem Histopathology. J Alzheimers Dis. 2016 Mar 31;52(3):863-73. doi: 10.3233/JAD-150732. [PubMed:27031469]

Drug created on October 01, 2015 13:41 / Updated on November 09, 2017 04:46