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Sunday, 3 November 2013

New Drug Approvals 2013 - Pt. XVII - Flutemetamol F18 (VizamylTM)

ATC Code: V09AX04

On October 25th, the FDA approved Flutemetamol F18 (Tradename: Vizamyl; Research Code: [18F]AH110690 ), a radioactive diagnostic agent, for intravenous (i.v.) use in Positron Emission Tomography (PET) imaging of the brain in adult patients with cognitive impairment, who are being evaluated for Alzheimer’s disease (AD) and dementia.

Alzheimer's disease is a non-treatable, progressively worsening and fatal disease, characterised by a decrease in cognitive functions, such as memory, and is usually associated with an accumulation of β amyloid (Uniprot: P05067) plaques in several brain regions. These deposits are believed to be responsible for cellular damage and ultimately cell death.

Flutemetamol F18 is the second approved diagnostic drug to estimate β-amyloid neuritic plaque density, after the approval of Florbetapir F18 in 2012. Like Florbetapir F18, Flutemetamol F18 binds to β amyloid plaques in the brain where the F-18 isotope produces a positron signal that can be detected by a PET scanner. The advantages of this compound over its predecessor are: exposure to a lower dose of radiation; and more time for PET image acquisition (20 vs. 10 minutes). In in vitro binding studies using postmortem human brain homogenates containing fibrillar β amyloid, the dissociation constant (Kd) for flutemetamol was 6.7 nM.

It is worth mentioning, that a positive scan, indicating the presence of β amyloid deposits, it's not enough to diagnose a patient with Alzheimer's disease, since these protein deposits can also be present in patients with other types of dementia, or in elderly people without any neurological disease. However, a negative scan, where little or none β-amyloid plaques can be detected, indicates that the cause for dementia is probably not due to Alzheimer's disease.

Flutemetamol F18 (IUPAC Name: 2-[3-fluoranyl-4-(methylamino)phenyl]-1,3-benzothiazol-6-ol; Canonical smiles: CNc1ccc(cc1[18F])c2nc3ccc(O)cc3s2 ; ChEMBL: CHEMBL2042122; PubChem: 15950376; ChemSpider: 13092196; Standard InChI Key: VVECGOCJFKTUAX-HUYCHCPVSA-N) is a synthetic small molecule with a radioactive isotope of fluorine (18F), with a molecular weight of 274.3 Da, 3 hydrogen bond acceptors, 2 hydrogen bond donors, and has an ALogP of 3.61. The compound is therefore fully compliant with the rule of five.

Flutemetamol F18 is available as a radioactive solution for intravenous injection and the recommended imaging dose is 185 megabecquerels (MBq) [5 millicuries(mCi)] in a total volume of 10 mL or less. Following intravenous injection, the plasma concentrations declines by approximately 75% in the first 20 minutes post-injection, and by approximately 90% in the first 180 minutes. Flutemetamol F18 metabolites are primarily excreted via the hepatobiliary (52%) and the renal system (37%).

The license holder for VizamylTM is GE Healthcare, and the full prescribing information can be found here.

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