Identification

Name
Flortaucipir F-18
Accession Number
DB14914
Type
Small Molecule
Groups
Approved, Investigational
Description

Flortaucipir F-18, also known as 18F-T807 and 18F-AV-1451, is a small indole molecule synthesized with a radioactive fluorine isotope.1 It is used as a marker in positron emission tomography (PET) imaging of patients suspected of having Alzheimer's disease. After crossing the blood-brain barrier, flortaucipir F-18 binds to aggregated tau protein, a hallmark of Alzheimer's disease whose incidence correlates well with disease progression.1,2,3

Although flortaucipir F-18 displays low levels of background binding throughout the brain,2 it does display off-target binding to monoamine oxidase MAO-A and MAO-B, as well as to regions containing high levels of melanin, neuromelanin, and iron.4,5. It was approved by the FDA on May 28, 2020, for sale by Avid Radiopharmaceuticals under the name TAUVID™ and is the first FDA-approved molecule for imaging aggregated tau protein in the brain.6

Structure
Thumb
Synonyms
  • Flortaucipir (18F)
  • Flortaucipir F 18
External IDs
(18F)AV 1451 / (F-18)T807 / 18F-AV-1451 / LY 3191748 / LY-3191748 / T-807 F-18 / T807 F-18
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TauvidInjection, solution51 mCi/1mLIntravenousEli Lilly and Company2020-05-28Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories
UNII
T1JP1KYU9O
CAS number
1522051-90-6
Weight
Average: 262.278
Monoisotopic: 262.088410001
Chemical Formula
C16H10FN3
InChI Key
GETAAWDSFUCLBS-SJPDSGJFSA-N
InChI
InChI=1S/C16H10FN3/c17-16-4-2-11(8-19-16)10-1-3-12-13-9-18-6-5-14(13)20-15(12)7-10/h1-9,20H/i17-1
IUPAC Name
2-(¹⁸F)fluoro-5-{5H-pyrido[4,3-b]indol-7-yl}pyridine
SMILES
[18F]C1=CC=C(C=N1)C1=CC=C2C(NC3=C2C=NC=C3)=C1

Pharmacology

Indication

Flortaucipir F-18 is a radioactive agent indicated for positron emission tomography (PET) imaging of aggregated tau neurofibrillary tangles (NFTs) in adult patients under evaluation for Alzheimer's disease. Flortaucipir F-18 is not indicated for use in patients under evaluation for chronic traumatic encephalopathy.6

Associated Conditions
Pharmacodynamics

Flortaucipir F-18 is a radioactive molecule that binds to and accumulates in tau NFT deposits allowing for imaging detection; however, non-specific binding and other factors allow for the possibility of misdiagnosis. As Flortaucipir F-18 is a radioactive substance, standard precautionary measures for protecting both patients and health care workers are advised. The safety and efficacy of flortaucipir F-18 in patients being evaluated for chronic traumatic encephalopathy are unknown and hence is not recommended.6

Mechanism of action

Alzheimer's disease is a progressive neurodegenerative disease characterized by the build-up of hyperphosphorylated tau protein aggregates. Hyperphosphorylated tau forms dimers termed paired helical filaments (PHFs), which aggregate further to form neurofibrillary tangles (NFTs) associated with neurodegeneration and severity of Alzheimer's symptoms.1,2

Flortaucipir F-18 is a small molecule that contains radioactive 18F, which decays by positron emission to 18O with a half-life of 109.8 minutes.6 As a small relatively lipophilic molecule, flortaucipir F-18, following intravenous injection, quickly passes through systemic circulation, crosses the blood-brain barrier, and binds to NFTs. Once bound, the ensuing radioactive decay emits pairs of 511 keV gamma photons useful in diagnostic imaging. The pattern and intensity of emission during imaging is used in the diagnosis of Alzheimer's disease.2,6

TargetActionsOrganism
AMicrotubule-associated protein tau
binder
Humans
NAmine oxidase [flavin-containing] A
binder
Humans
NAmine oxidase [flavin-containing] B
binder
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Flortaucipir F-18 is administered as an intravenous bolus injection, 6 and peak brain uptake in mice of 4.16% ID/g is achieved by 2 minutes.2 Fast transfer from the peripheral circulation to the brain was corroborated by human studies that demonstrated peak SUV in gray matter >2 across subjects approximately 5 minutes after administration.3

Pharmacokinetic studies in humans suggest that equilibrium is achieved by 55 minutes (Logan DVR) and by 80 - 100 minutes (SUVR),3 and current guidelines recommend initiating imaging approximately 80 minutes after initial administration.6

Volume of distribution

Flortaucipir F-18 injected into mice accumulates primarily in the kidneys (14.99 ± 0.39 %ID/g at five minutes and 5.52 ± 0.91 %ID/g at 30 minutes post-injection) and liver (4.44 ± 0.16/5.99 ± 0.42 %ID/g at five/30 minutes, respectively). It is able to cross the blood-brain barrier, with relatively high penetration early (4.43 ± 0.91 %ID/g at five minutes) and low residual penetration later (0.62 ± 0.06 %ID/g at 30 minutes). Detectable amounts of Flortaucipir F-18 are found in the systemic circulation, as well as in muscle and bone.2

Protein binding
Not Available
Metabolism

Initial studies in mice described the parent compound and four uncharacterized metabolites, one of which, termed metabolite 1, is presumed to be [18F]fluoride. Plasma radioactivity corresponded only to the parent compound and metabolite 1. All metabolites were detected in the liver while all metabolites except metabolite 2 were found in the kidneys.2

Route of elimination

The major route of elimination for Flortaucipir F-18 is via the kidneys.2

Half life

Flortaucipir F-18 plasma half-life was calculated at 17.0 ± 4.2 minutes; correction for metabolite half-life yielded a biexponential distribution with half-lives of 18.1 ± 5.8 and 2.4 ± 0.5 minutes.3

Clearance
Not Available
Toxicity

Toxicity information regarding Flortaucipir F-18 is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as headaches and increased blood pressure. Symptomatic and supportive measures are recommended.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
No interactions found.

References

Synthesis Reference

Neil Vasdev, Timothy M. Shoup. "Radiosynthesis of tau radiopharmaceuticals." US patent US9546167B2, issued January 17, 2017.

General References
  1. Wang YT, Edison P: Tau Imaging in Neurodegenerative Diseases Using Positron Emission Tomography. Curr Neurol Neurosci Rep. 2019 Jun 6;19(7):45. doi: 10.1007/s11910-019-0962-7. [PubMed:31172290]
  2. Xia CF, Arteaga J, Chen G, Gangadharmath U, Gomez LF, Kasi D, Lam C, Liang Q, Liu C, Mocharla VP, Mu F, Sinha A, Su H, Szardenings AK, Walsh JC, Wang E, Yu C, Zhang W, Zhao T, Kolb HC: [(18)F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease. Alzheimers Dement. 2013 Nov;9(6):666-76. doi: 10.1016/j.jalz.2012.11.008. Epub 2013 Feb 12. [PubMed:23411393]
  3. Wooten DW, Guehl NJ, Verwer EE, Shoup TM, Yokell DL, Zubcevik N, Vasdev N, Zafonte RD, Johnson KA, El Fakhri G, Normandin MD: Pharmacokinetic Evaluation of the Tau PET Radiotracer (18)F-T807 ((18)F-AV-1451) in Human Subjects. J Nucl Med. 2017 Mar;58(3):484-491. doi: 10.2967/jnumed.115.170910. Epub 2016 Sep 22. [PubMed:27660144]
  4. Vermeiren C, Motte P, Viot D, Mairet-Coello G, Courade JP, Citron M, Mercier J, Hannestad J, Gillard M: The tau positron-emission tomography tracer AV-1451 binds with similar affinities to tau fibrils and monoamine oxidases. Mov Disord. 2018 Feb;33(2):273-281. doi: 10.1002/mds.27271. Epub 2017 Dec 26. [PubMed:29278274]
  5. Choi JY, Cho H, Ahn SJ, Lee JH, Ryu YH, Lee MS, Lyoo CH: Off-Target (18)F-AV-1451 Binding in the Basal Ganglia Correlates with Age-Related Iron Accumulation. J Nucl Med. 2018 Jan;59(1):117-120. doi: 10.2967/jnumed.117.195248. Epub 2017 Aug 3. [PubMed:28775201]
  6. FDA Approved Drug Products: Tauvid (flortaucipir F-18) injection [Link]
External Links
ChemSpider
32701063
ChEMBL
CHEMBL3545253
Wikipedia
Flortaucipir_(18F)
FDA label
Download (1.05 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingDiagnosticCognition Disorders1
1CompletedBasic ScienceAlzheimer's Disease (AD)1
1CompletedDiagnosticAlzheimer's Disease (AD)4
1CompletedDiagnosticCorticobasal Degeneration / Progressive Supranuclear Palsy (PSP)1
1CompletedDiagnosticFrontotemporal Dementia1
1RecruitingDiagnosticPrimary Progressive Aphasia With Suspected Alzheimer's Disease / Progressive Primary Aphasia1
1TerminatedDiagnosticCognitive Decline1
1WithdrawnDiagnosticTraumatic Brain Injury (TBI)1
2Active Not RecruitingDiagnosticAlzheimer's Disease (AD)3
2Active Not RecruitingDiagnosticAlzheimer's Disease (AD) / Depression / Traumatic Brain Injury (TBI)1
2Active Not RecruitingDiagnosticAlzheimer's Disease (AD) / Human Immunodeficiency Virus (HIV) Infections1
2Active Not RecruitingDiagnosticAlzheimer's Disease (AD) / Progressive Posterior Cortical Dysfunction (PPCD)1
2Active Not RecruitingDiagnosticAmyotrophic Lateral Sclerosis (ALS)1
2CompletedDiagnosticAlzheimer's Disease (AD)4
2CompletedDiagnosticChronic Traumatic Encephalopathy (CTE)1
2CompletedDiagnosticFrontotemporal Dementia / Frontotemporal Dementia (FTD) / Frontotemporal Lobar Degeneration / Frontotemporal Lobar Degeneration (FTLD) / FTD / FTLD / Tauopathies1
2Not Yet RecruitingDiagnosticAlzheimer's Disease (AD)1
2WithdrawnDiagnosticAlzheimer's Disease (AD)1
2, 3CompletedDiagnosticAlzheimer's Disease (AD)1
3CompletedDiagnosticAlzheimer's Disease (AD)2
4Enrolling by InvitationDiagnosticAlzheimer's Disease (AD) / Dementia, Vascular / Diffuse Lewy Body Disease / Frontotemporal Dementia1
4Enrolling by InvitationDiagnosticBrain Imaging / Whole Body Imaging1
Not AvailableActive Not RecruitingNot AvailableMCI / Normal Controls1
Not AvailableCompletedNot AvailableAlzheimer's Disease (AD) / Early Mild Cognitive Impairment (EMCI) / Late Mild Cognitive Impairment (LMCI) / Mild Cognitive Impairment (MCI) / Significant Memory Concern (SMC)1
Not AvailableRecruitingNot AvailableAlzheimer's Disease (AD) / Early Onset Alzheimer Disease / Mild Cognitive Impairment (MCI)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solutionIntravenous51 mCi/1mL
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
PropertyValueSource
logP1.67Xia et al 2013
Predicted Properties
PropertyValueSource
Water Solubility0.0111 mg/mLALOGPS
logP3.52ALOGPS
logP2.84ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)13.03ChemAxon
pKa (Strongest Basic)8.13ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area41.57 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity75.53 m3·mol-1ChemAxon
Polarizability27.23 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Binder
Curator comments
Flortaucipir F-18 binds to aggregated tau proteins including paired helical filaments (PHFs) with a Kd of 0.57 nM.
General Function
Structural constituent of cytoskeleton
Specific Function
Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity. The C-terminus binds axonal microtubules while the N-terminus binds neu...
Gene Name
MAPT
Uniprot ID
P10636
Uniprot Name
Microtubule-associated protein tau
Molecular Weight
78927.025 Da
References
  1. Wang YT, Edison P: Tau Imaging in Neurodegenerative Diseases Using Positron Emission Tomography. Curr Neurol Neurosci Rep. 2019 Jun 6;19(7):45. doi: 10.1007/s11910-019-0962-7. [PubMed:31172290]
  2. Xia CF, Arteaga J, Chen G, Gangadharmath U, Gomez LF, Kasi D, Lam C, Liang Q, Liu C, Mocharla VP, Mu F, Sinha A, Su H, Szardenings AK, Walsh JC, Wang E, Yu C, Zhang W, Zhao T, Kolb HC: [(18)F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease. Alzheimers Dement. 2013 Nov;9(6):666-76. doi: 10.1016/j.jalz.2012.11.008. Epub 2013 Feb 12. [PubMed:23411393]
  3. Wooten DW, Guehl NJ, Verwer EE, Shoup TM, Yokell DL, Zubcevik N, Vasdev N, Zafonte RD, Johnson KA, El Fakhri G, Normandin MD: Pharmacokinetic Evaluation of the Tau PET Radiotracer (18)F-T807 ((18)F-AV-1451) in Human Subjects. J Nucl Med. 2017 Mar;58(3):484-491. doi: 10.2967/jnumed.115.170910. Epub 2016 Sep 22. [PubMed:27660144]
  4. Vermeiren C, Motte P, Viot D, Mairet-Coello G, Courade JP, Citron M, Mercier J, Hannestad J, Gillard M: The tau positron-emission tomography tracer AV-1451 binds with similar affinities to tau fibrils and monoamine oxidases. Mov Disord. 2018 Feb;33(2):273-281. doi: 10.1002/mds.27271. Epub 2017 Dec 26. [PubMed:29278274]
  5. FDA Approved Drug Products: Tauvid (flortaucipir F-18) injection [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Serotonin binding
Specific Function
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
Gene Name
MAOA
Uniprot ID
P21397
Uniprot Name
Amine oxidase [flavin-containing] A
Molecular Weight
59681.27 Da
References
  1. Vermeiren C, Motte P, Viot D, Mairet-Coello G, Courade JP, Citron M, Mercier J, Hannestad J, Gillard M: The tau positron-emission tomography tracer AV-1451 binds with similar affinities to tau fibrils and monoamine oxidases. Mov Disord. 2018 Feb;33(2):273-281. doi: 10.1002/mds.27271. Epub 2017 Dec 26. [PubMed:29278274]
  2. FDA Approved Drug Products: Tauvid (flortaucipir F-18) injection [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Primary amine oxidase activity
Specific Function
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
Gene Name
MAOB
Uniprot ID
P27338
Uniprot Name
Amine oxidase [flavin-containing] B
Molecular Weight
58762.475 Da
References
  1. Vermeiren C, Motte P, Viot D, Mairet-Coello G, Courade JP, Citron M, Mercier J, Hannestad J, Gillard M: The tau positron-emission tomography tracer AV-1451 binds with similar affinities to tau fibrils and monoamine oxidases. Mov Disord. 2018 Feb;33(2):273-281. doi: 10.1002/mds.27271. Epub 2017 Dec 26. [PubMed:29278274]
  2. FDA Approved Drug Products: Tauvid (flortaucipir F-18) injection [Link]

Drug created on May 20, 2019 08:34 / Updated on June 12, 2020 10:53

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