| Size | Price | Stock | Qty |
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| 5mg |
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| 25mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
PET tracer for tau protein
Paired helical filament tau (PHF-tau) in Alzheimer's disease brains (Kd = 14.6 nM, determined by saturation binding using human AD brain sections). Selective over amyloid β (Aβ) plaques (>25-fold selectivity as assessed by autoradiography signal intensity ratios). [1] |
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| ln Vitro |
One important neuropathological substrate in the pathogenesis of neurodegenerative disorders like Alzheimer's disease (AD) is aggregated tau protein. Results from in vitro radiation self-healing demonstrate that PHF-tau positive human brain slices bind to [18F] T807 with a strong force (Kd=14.6nM). It was observed that [18F]T807 binding colocalized with immunoreactive PHF-tau pathology but did not highlight Ab plaques on antagonist sections when autoradiographic and double immunohistochemical staining of PHF-tau and Ab were compared [1]. [18F] T807 binds tightly to tau lesions, which are mainly made up of pairs of helical filaments and are found in the brains of Alzheimer's patients. These lesions include dystrophic neurites and neuronal outer tangles. In Arduino, [18F] T807 binds off-target to cells that contain melanophore and neuromelanin, as well as to cerebral thrombotic effects [2].
Flortaucipir ([¹⁸F]T807) exhibits strong and specific binding to native PHF-tau aggregates in human Alzheimer's disease (AD) brain sections as demonstrated by in vitro autoradiography. Binding colocalized with immunoreactive PHF-tau pathology (tau tangles, neuropil threads, neuritic plaques) but did not highlight Aβ plaques in adjacent sections. The dissociation constant (Kd) for binding to PHF-tau, determined by Scatchard plot analysis of saturation binding data using human AD brain sections, was 14.6 nM. Autoradiography signals from [¹⁸F]T807 in the gray matter of PHF-tau-rich brain sections were 25.7 times higher than in sections with Aβ plaques but poor PHF-tau. A fluorescent analog, T726 (structurally related to T807), showed positive staining that colocalized with PHF-tau immunostaining but not with Aβ plaques in a triple-staining assay on human brain sections. [1] |
| ln Vivo |
In mouse models, [18F] T807 can cross the blood-brain barrier and vanish quickly. With activity values ranging from 4.43% ID/g at 5 minutes to 0.62% ID/g at 30 minutes, [18F] T807 is rapidly eliminated from the brain. Elimination: Elimination is a crucial clearance process that causes the maximal concentration of tracer in the interference to drop to 5.52% ID/g after 30 minutes from 14.99% ID/g at the 5-minute mark. During a PET scan, the amount of activity that builds up in the bones and anatomy is comparatively minimal [1].
In vivo PET imaging in normal mice demonstrated that [¹⁸F]T807 efficiently crosses the blood-brain barrier, shows rapid brain penetration (peak uptake of 4.16 ± 0.32 %ID/g at 2 minutes post-injection), and undergoes fast washout from the brain, clearing to skeletal muscle levels in about 25-30 minutes. The tracer was also tested in APPSWE-Tau transgenic mice; however, no noticeable difference in retention or maximum uptake was observed compared to wild-type mice, suggesting it does not bind to the tau aggregates present in this particular mouse model. [1] |
| Enzyme Assay |
To screen potential tau binders, human AD brain sections were used as a source of native paired helical filament (PHF)-tau and Aβ rather than synthetic tau aggregates or Aβ fibrils generated in vitro to measure the affinity and selectivity of [(18)F]T807 to tau and Aβ. In vitro autoradiography results show that [(18)F]T807 exhibits strong binding to PHF-tau-positive human brain sections. A dissociation constant (Kd) of [(18)F]T807 (14.6 nM) was measured using brain sections from the frontal lobe of AD patients. A comparison of autoradiography and double immunohistochemical staining of PHF-tau and Aβ on adjacent sections demonstrated that [(18)F]T807 binding colocalized with immunoreactive PHF-tau pathology, but did not highlight Aβ plaques[1].
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| Cell Assay |
We applied [F-18]-AV-1451 phosphor screen autoradiography, [F-18]-AV-1451 nuclear emulsion autoradiography, and [H-3]-AV-1451 in vitro binding assays to the study of postmortem samples from patients with a definite pathological diagnosis of Alzheimer disease, frontotemporal lobar degeneration-tau, frontotemporal lobar degeneration-transactive response DNA binding protein 43 (TDP-43), progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies, multiple system atrophy, cerebral amyloid angiopathy and elderly controls free of pathology[2].
For qualitative assessment of tau binding by fluorescent analogs, frozen human brain sections (10 μm) were fixed and then incubated with 100 μM of the test fluorescent compound (e.g., T726) in 50% ethanol/PBS for 1 hour at room temperature. After washing, the sections were blocked and subjected to double immunohistochemical staining for PHF-tau and Aβ₄₂. Colocalization of compound staining with antibody signals was assessed by overlaying images from stained serial tissue sections using microscopy. [1] |
| Animal Protocol |
In vivo studies in mice demonstrated that [(18)F]T807 was able to cross the blood-brain barrier and washed out quickly.
Conclusions: [(18)F]T807 demonstrates high affinity and selectivity to PHF-tau as well as favorable in vivo properties, making this a promising candidate as an imaging agent for AD.[2] For brain uptake PET imaging, normal mice were anesthetized and placed on a scanner bed. A high-resolution CT scan was performed for anatomical registration, followed by a 30-minute PET scan. Within 3 minutes after the start of the PET acquisition, [¹⁸F]T807 (250 μCi in 200 μL saline) was administered via tail vein injection. PET images were generated for each minute of acquisition. For biodistribution and excretion studies, mice were administered 250 μCi of [¹⁸F]T807 (in 200 μL saline) via tail vein injection. At 5, 15, and 30 minutes post-injection, animals were anesthetized. Blood was collected via cardiac puncture, and plasma was separated. After euthanasia, organs (liver, kidneys, skeletal muscle, brain, bone) were harvested, weighed, and their radioactivity was measured using a gamma counter to calculate % injected dose per gram (%ID/g). For biostability studies, mice were administered 300 μCi of [¹⁸F]T807 (in ≤200 μL saline) via tail vein injection and sacrificed at 10 and 30 minutes. Plasma, urine, brain, kidneys, and liver were collected. Tissues were homogenized. Samples (plasma, urine, tissue homogenates) were mixed with chloroform/methanol, centrifuged to separate organic and aqueous fractions, and both fractions were assayed for radioactivity. Metabolite analysis was performed by HPLC with a radiometric detector. [1] |
| ADME/Pharmacokinetics |
In mice, [¹⁸F]T807 exhibited rapid brain uptake and clearance. Peak brain uptake was observed at 4.16 ± 0.32 %ID/g at 2 min, decreasing to 0.62 ± 0.06 %ID/g at 30 min. Biodistribution data showed high initial uptake in the kidneys (14.99 ± 0.39 %ID/g at 5 min) and liver (14.44 ± 0.16 %ID/g at 5 min), indicating primary clearance via these organs. Relatively low but still present activity in bone suggested possible partial defluorination in vivo. Mouse metabolic studies identified four metabolites, all with shorter HPLC retention times than the parent tracer. Only the parent tracer was detected in the brain homogenate at 10 and 30 min (1.15 %ID/g and 0.32 %ID/g, respectively). At 10 minutes, 34% of the radioactivity in the plasma was intact parent radioactive material, and 66% was a metabolite presumed to be [¹⁸F] fluoride. At 30 minutes, the main component of the plasma was [¹⁸F] fluoride. The tracer and its metabolites were mainly eliminated by the kidneys and urine. The LogP (octanol/water partition coefficient) of T807 was measured to be 1.67. [1]
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| Toxicity/Toxicokinetics |
T807 (a non-radioactive compound) was screened against 72 common central nervous system targets (receptors, channels, transporters, and enzymes). At a screening concentration of 10 μM, it showed an inhibition rate of >50% against five targets: human norepinephrine transporter (NET) (IC₅₀ = 2.2 μM), rabbit monoamine transporter, rat glutamate receptor (IC₅₀ = 2.7 μM), NMDA receptor, and human μ-opioid receptor (inhibition rate of 31% at 1 μM concentration, IC₅₀ value not determined). At a concentration of 1 μM, it had no inhibitory effect on monoamine oxidase A (MAO-A) or MAO-B. The IC₅₀ for acetylcholinesterase was 6 μM. The authors point out that the maximum human dose of T807 in imaging applications is very low (approximately 13 μg at a 10 mCi dose), therefore the likelihood of adverse reactions from inhibiting these central nervous system targets is considered very low. [1]
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| References | |
| Additional Infomation |
Flortaucipir is being investigated in the clinical trial NCT03507257 (Longitudinal Early-Onset Alzheimer's Disease Study Protocol). Flortaucipir ([¹⁸F]T807) is a novel positron emission tomography (PET) imaging agent (radiopharmaceutical) designed for in vivo visualization of neurofibrillary tangles composed of paired helical tau proteins (PHF-tau) in Alzheimer's disease. It belongs to the 5H-pyrido[4,3-b]indole class and was discovered by screening compounds directly on natural human Alzheimer's disease brain tissue sections, rather than using synthetic tau protein aggregates, which have been shown to be unreliable. This radiotracer can be synthesized with high radiochemical yield (47% decay correction) and purity (>99%), and possesses a high specific activity (9.63 Ci/μmol).
As of now, while publishing this research, it is undergoing a Phase 0 clinical trial to explore its potential in imaging human Alzheimer's disease. There are also studies suggesting that it may have potential in imaging other tau protein diseases, such as progressive supranuclear palsy and corticobasal degeneration. [1] |
| Molecular Formula |
C₁₆H₁₀FN₃
|
|---|---|
| Molecular Weight |
263.2691
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| Exact Mass |
263.086
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| Elemental Analysis |
C, 72.99; H, 3.83; F, 7.22; N, 15.96
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| CAS # |
1415379-56-4
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| PubChem CID |
71059746
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| Appearance |
Typically exists as off-white to yellow solids at room temperature
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| LogP |
3.917
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
20
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| Complexity |
351
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1C([H])=C([H])C(=C([H])N=1)C1C([H])=C([H])C2C3C([H])=NC([H])=C([H])C=3N([H])C=2C=1[H]
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| InChi Key |
GETAAWDSFUCLBS-UHFFFAOYSA-N
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| InChi Code |
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
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| Chemical Name |
5H-Pyrido(4,3-b)indole, 7-(6-fluoro-3-pyridinyl)-
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| Synonyms |
AV-1451; AV 1451; AV1451; Flortaucipir;T-807; T807; T 807
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 16.6 mg/mL (~63.05 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 1.25 mg/mL (4.75 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.25 mg/mL (4.75 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7984 mL | 18.9919 mL | 37.9838 mL | |
| 5 mM | 0.7597 mL | 3.7984 mL | 7.5968 mL | |
| 10 mM | 0.3798 mL | 1.8992 mL | 3.7984 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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