Flutemetamol F18 (Vizamyl), PET agent used for diagnosis of Alzheimer''s disease

Physicochemical Properties

Molecular Formula	C14H11FN2OS
Molecular Weight	273.315880060196
Exact Mass	273.06
CAS #	765922-62-1
PubChem CID	15950376
Appearance	Typically exists as solid at room temperature
LogP	3.922
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	2
Heavy Atom Count	19
Complexity	320
Defined Atom Stereocenter Count	0
SMILES	S1C2C=C(C=CC=2N=C1C1C=CC(=C(C=1)[18F])NC)O
InChi Key	VVECGOCJFKTUAX-HUYCHCPVSA-N
InChi Code	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
Chemical Name	2-[3-(18F)fluoranyl-4-(methylamino)phenyl]-1,3-benzothiazol-6-ol
HS Tariff Code	2934.99.9001
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)

Biological Activity

ADME/Pharmacokinetics	Absorption, Distribution and Excretion 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. Excretion was found to be approximately 37% renal and 52% hepatobiliary. Metabolism / Metabolites The F 18 in circulation during the 30-120 minutes imaging window in plasma was principally associated with flutemetamol metabolites.
Toxicity/Toxicokinetics	Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Information in this record refers to the use of flutemetamol F 18 as a diagnostic agent. No information is available on the use of flutemetamol F 18 during breastfeeding. The manufacturer recommends withholding breastfeeding for 24 hours after a diagnostic dose of 185 MBq (5 mCi). This length of time is about 10 half-lives of fluoride F 18 and less than 0.01% of the radioactivity administered will remain in the body. The mother can nurse just before administration of the radiopharmaceutical. If the mother has expressed and saved milk prior to the examination, she can feed it to the infant during the period of nursing interruption. Mothers concerned about the level of radioactivity in their milk could ask to have it tested at a nuclear medicine facility at their hospital. When the radioactivity is at a safe level she may resume breastfeeding. A method for measuring milk radioactivity and determining the time when a mother can safely resume breastfeeding has been published. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date.
Additional Infomation	Flutemetamol ((18)F) is a member of the class of benzothiazoles that is 1,3-benzothiazole substituted by 3-((18)F)fluoro-4-(methylamino)phenyl and hydroxy groups at positions 3 and 6 respectively. A positron emission tomography imaging ligand for the detection of amyloid aggregation associated with Alzheimer disease. It has a role as a radioactive imaging agent. It is a (18)F radiopharmaceutical, a member of benzothiazoles, an aromatic amine and a secondary amino compound. 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. Flutemetamol f-18 is a Radioactive Diagnostic Agent. The mechanism of action of flutemetamol f-18 is as a Radiopharmaceutical Activity. Flutemetamol F 18 is a radiopharmaceutical containing flutemetamol, a thioflavin derivative of Pittsburgh compound B (PiB) labeled with the radioisotope fluorine F18 that can be used to detect beta-amyloid deposition upon positron emission tomography (PET). After intravenous administration of flutemetamol F 18, the flutemetamol moiety selectively accumulates in and binds to cerebral fibrillar amyloid-beta in the brain. The fluorine F18 radioisotope moiety is detected using PET, which allows imaging and quantification of amyloid-beta density. Amyloid plaque deposition is linked to cognitive decline, including Alzheimer's disease, and may be linked to chemotherapy-induced cognitive impairment (CICI). Drug 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. FDA Label This medicinal product is for diagnostic use only. Vizamyl is a radiopharmaceutical medicinal product indicated for Positron Emission Tomography (PET) imaging of β 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. Vizamyl should be used in conjunction with a clinical evaluation. A negative scan indicates sparse or no plaques, which is not consistent with a diagnosis of AD. Diagnosis of Alzheimer's disease 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).

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.6587 mL	18.2936 mL	36.5872 mL
	5 mM	0.7317 mL	3.6587 mL	7.3174 mL
	10 mM	0.3659 mL	1.8294 mL	3.6587 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.