Identification
NameFlorbetapir (18F)
Accession NumberDB09149
TypeSmall Molecule
GroupsApproved
Description

Florbetapir (18F) is a radiopharmaceutical compound containing the radionuclide fluorine-18 bound to the compound florbetapir, a molecule that binds with high affinity to beta amyloid plaque, a peptide that plays a key role in Alzheimer's Disease pathogenesis. Marketed as the product Amyvid, florbetapir 18F 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) and other causes of cognitive decline.

The radionucleide fluorine-18 was chosen as it has a half life of 110 minutes allowing it to accumulate sufficiently in the brain before undergoing positon emission decay.

Structure
Thumb
Synonyms
[18F]Florbetapir
4-{(E)-2-[6-(2-{2-[2-(18F)fluoroethoxy]ethoxy}ethoxy)pyridin-3-yl]ethenyl}-N-methylaniline
Florbetapir F-18
Florbetapir F18
florbetapir-fluorine-18
External IDs (18F)AV-45 / 18F-AV-45 / 18FAV-45 / 18FAV45 / AV-45 F-18
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AmyvidInjection, solution800 MBq/mlIntravenousEli Lilly Nederland B.V.2013-01-14Not applicableEu
AmyvidInjection, solution1900 MBq/mlIntravenousEli Lilly Nederland B.V.2013-01-14Not applicableEu
AmyvidInjection, solution800 MBq/mlIntravenousEli Lilly Nederland B.V.2013-01-14Not applicableEu
AmyvidInjection, solution51 mCi/mLIntravenousEli Lilly & Co. Ltd.2012-06-01Not applicableUs
AmyvidInjection, solution1900 MBq/mlIntravenousEli Lilly Nederland B.V.2013-01-14Not applicableEu
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNII6W15Z5R0RU
CAS number956103-76-7
WeightAverage: 359.432
Monoisotopic: 359.18745534
Chemical FormulaC20H25FN2O3
InChI KeyYNDIAUKFXKEXSV-CRYLGTRXSA-N
InChI
InChI=1S/C20H25FN2O3/c1-22-19-7-4-17(5-8-19)2-3-18-6-9-20(23-16-18)26-15-14-25-13-12-24-11-10-21/h2-9,16,22H,10-15H2,1H3/b3-2+/i21-1
IUPAC Name
4-[(E)-2-[6-(2-{2-[2-(¹⁸F)fluoroethoxy]ethoxy}ethoxy)pyridin-3-yl]ethenyl]-N-methylaniline
SMILES
[H]N(C1=C([H])C([H])=C(\C([H])=C(/[H])C2=C([H])N=C(OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])[18F])C([H])=C2[H])C([H])=C1[H])C([H])([H])[H]
Pharmacology
Indication

Florbetapir 18F 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) and other causes of cognitive decline.

Structured Indications
Pharmacodynamics

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

Mechanism of action

Florbetapir (18F) is a radiopharmaceutical compound containing the radionuclide fluorine-18 bound to the compound florbetapir, a molecule that binds with high affinity to beta amyloid plaque, a peptide that plays a key role in Alzheimer's Disease pathogenesis. The radionucleide fluorine-18 was chosen as it has a half life of 110 minutes allowing it to accumulate sufficiently in the brain before undergoing positon emission decay.

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

The time-activity curves for florbetapir F 18 in the brain of subjects with positive scans show continual signal increases from time zero through 30 minutes post-administration, with stable values thereafter up to at least 90 minutes post-injection. Following the intravenous administration of 370 MBq (10 mCi) of florbetapir F 18 to healthy volunteers, the drug was distributed throughout the body with less than 5% of the injected F 18 radioactivity present in the blood by 20 minutes following administration, and less than 2% present by 45 minutes after administration.

Volume of distributionNot Available
Protein bindingNot Available
Metabolism

The residual F 18 in circulation during the 30-90 minute imaging window was principally in the form of polar F 18 metabolites. Essentially all radioactivity collected in the urine was present as polar metabolites of florbetapir F 18. Three metabolites have been discovered and identified as [18F]AV-160 (desmethyl-[18F]AV-45), [18F]AV-267 (N-acetyl–[18F]AV-160), and an [18F]-Polar species, the identity of which has not been confirmed. Additionally, although metabolites may make some contribution to signal detection, particularly to the nontarget activity, it is concluded that there will be minimal interference from these radiolabeled metabolites to the amyloid target binding in the [18F]AV-45 brain PET image (Wong et al, 2010).

SubstrateEnzymesProduct
Florbetapir (18F)
Not Available
[18F]AV-160 (desmethyl-[18F]AV-45)Details
Florbetapir (18F)
Not Available
[18F]AV-267 (N-acetyl–[18F]AV-160)Details
Florbetapir (18F)
Not Available
[18F]-Polar speciesDetails
Route of elimination

Whole body scanning following the intravenous injection showed accumulation of radioactivity in the liver within four minutes post-injection, followed by elimination of the radioactivity predominantly through the biliary/gastrointestinal tract with much lower radioactivity detected in the bladder. Essentially all radioactivity collected in the urine was present as polar metabolites of florbetapir F 18.

Half lifeNot Available
ClearanceNot Available
Toxicity

The most common reported adverse reaction was headache, occurring in 2% of patients, followed by musculoskeletal pain, blood pressure increased, fatigue, nausea, and injection site reaction, all occurring in <1% of patients.

Affected organismsNot Available
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions Not Available
Food InteractionsNot Available
References
Synthesis Reference

Wong DF, Rosenberg PB, Zhou Y, Kumar A, Raymont V, Ravert HT, Dannals RF, Nandi A, Brasic JR, Ye W, Hilton J, Lyketsos C, Kung HF, Joshi AD, Skovronsky DM, Pontecorvo MJ: In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18F-AV-45 (florbetapir [corrected] F 18). J Nucl Med. 2010 Jun;51(6):913-20. doi: 10.2967/jnumed.109.069088.

#Fowler J. S. and Wolf A. P. (1982) The synthesis of carbon-11, fluorine-18 and nitrogen-13 labeled radiotracers for biomedical applications. Nucl. Sci. Ser. Natl Acad. Sci. Natl Res. Council Monogr. 1982.

General References
  1. Wong DF, Rosenberg PB, Zhou Y, Kumar A, Raymont V, Ravert HT, Dannals RF, Nandi A, Brasic JR, Ye W, Hilton J, Lyketsos C, Kung HF, Joshi AD, Skovronsky DM, Pontecorvo MJ: In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18F-AV-45 (florbetapir [corrected] F 18). J Nucl Med. 2010 Jun;51(6):913-20. doi: 10.2967/jnumed.109.069088. [PubMed:20501908 ]
  2. Choi SR, Golding G, Zhuang Z, Zhang W, Lim N, Hefti F, Benedum TE, Kilbourn MR, Skovronsky D, Kung HF: Preclinical properties of 18F-AV-45: a PET agent for Abeta plaques in the brain. J Nucl Med. 2009 Nov;50(11):1887-94. doi: 10.2967/jnumed.109.065284. Epub 2009 Oct 16. [PubMed:19837759 ]
External Links
ATC CodesV09AX05 — Florbetapir (18f)
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (4.31 MB)
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedDiagnosticAlzheimer's Disease (AD)1
0RecruitingOtherAlzheimer's Disease (AD) / Healthy Volunteers1
0RecruitingOtherAlzheimer's Disease (AD) / Healthy Volunteers / Progressive Supranuclear Palsy (PSP)2
1CompletedNot AvailableAlzheimer's Disease (AD) / Chronic Traumatic Encephalopathy (CTE) / Frontal Temporal Dementia (FTD) / Parkinson's Disease (PD) / Pick's Disease / Progressive Supranuclear Palsy (PSP) / Tauopathies1
1CompletedDiagnosticAlzheimer's Disease (AD)5
1CompletedDiagnosticCorticobasal Degeneration / Progressive Supranuclear Palsy (PSP)1
1CompletedOtherAlzheimer's Disease (AD)1
1RecruitingDiagnosticAlzheimer's Disease (AD)1
1RecruitingDiagnosticFrontotemporal Dementia1
1, 2CompletedDiagnosticAlzheimer's Disease (AD) / Diffuse Lewy Body Disease / Parkinson's Disease (PD)1
2CompletedDiagnosticAlzheimer's Disease (AD)2
2CompletedDiagnosticAlzheimer's Disease (AD) / Frontotemporal Dementia1
2CompletedDiagnosticAlzheimer's Disease (AD) / Mild Cognitive Impairment (MCI)2
2CompletedDiagnosticChronic Traumatic Encephalopathy (CTE)1
2CompletedDiagnosticParkinson's Disease (PD)1
2RecruitingDiagnosticAlzheimer's Disease (AD) / Mild Cognitive Impairment (MCI) / Neurodegenerative Disorders1
2WithdrawnTreatmentDementia Alzheimer's Type1
2, 3Active Not RecruitingDiagnosticAlzheimer's Disease (AD)1
2, 3CompletedDiagnosticAlzheimer's Disease (AD) / Mild Cognitive Impairment (MCI)1
3Active Not RecruitingTreatmentAlzheimer's Disease (AD)1
3CompletedDiagnosticAlzheimer's Disease (AD)2
3CompletedDiagnosticProgressive Cognitive Decline1
3RecruitingDiagnosticAlzheimer's Disease (AD) and Related Disorders1
4CompletedDiagnosticAlzheimer's Disease (AD)3
4CompletedDiagnosticAlzheimers Disease1
4RecruitingDiagnosticPostoperative Cognitive Dysfunction1
Not AvailableCompletedDiagnosticAlzheimer's Disease (AD)3
Not AvailableCompletedDiagnosticAlzheimer's Disease (AD) / Mild Cognitive Impairment (MCI) / Neurodegenerative Disorders1
Not AvailableRecruitingNot AvailableAlzheimer's Disease (AD) / Cognition Disorders1
Not AvailableRecruitingNot AvailableChronic Traumatic Encephalopathy (CTE) / Mild Cognitive Impairment (MCI) / Traumatic Brain Injury (TBI)1
Not AvailableRecruitingDiagnosticCardiac Amyloidosis1
Not AvailableRecruitingDiagnosticElderly / Major Depressive Disorder (MDD)1
Not AvailableUnknown StatusDiagnosticDisseminated Sclerosis1
Not AvailableWithdrawnDiagnosticAlzheimer's Disease (AD)1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, solutionIntravenous1900 MBq/ml
Injection, solutionIntravenous51 mCi/mL
Injection, solutionIntravenous800 MBq/ml
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7687052 No2007-04-302027-04-30Us
US8506929 No2007-04-302027-04-30Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0058 mg/mLALOGPS
logP3.61ALOGPS
logP3.11ChemAxon
logS-4.8ALOGPS
pKa (Strongest Basic)4.62ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area52.61 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity103.01 m3·mol-1ChemAxon
Polarizability40.43 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 styrenes. These are organic compounds containing an ethenylbenzene moiety.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassStyrenes
Direct ParentStyrenes
Alternative ParentsPhenylalkylamines / Secondary alkylarylamines / Alkyl aryl ethers / Pyridines and derivatives / Heteroaromatic compounds / Dialkyl ethers / Azacyclic compounds / Organofluorides / Hydrocarbon derivatives / Alkyl fluorides
SubstituentsStyrene / Phenylalkylamine / Alkyl aryl ether / Secondary aliphatic/aromatic amine / Pyridine / Heteroaromatic compound / Organoheterocyclic compound / Azacycle / Secondary amine / Dialkyl ether
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptorsorganofluorine compound, aromatic ether, substituted aniline, pyridines, fluorine-18 radiopharmaceutical (CHEBI:66880 )

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
References
  1. Choi SR, Golding G, Zhuang Z, Zhang W, Lim N, Hefti F, Benedum TE, Kilbourn MR, Skovronsky D, Kung HF: Preclinical properties of 18F-AV-45: a PET agent for Abeta plaques in the brain. J Nucl Med. 2009 Nov;50(11):1887-94. doi: 10.2967/jnumed.109.065284. Epub 2009 Oct 16. [PubMed:19837759 ]
Drug created on October 01, 2015 11:14 / Updated on July 25, 2017 17:57