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New Drug Approvals 2014 - Pt. VI - Florbetaben F18 (Neuraceq™)




ATC Code: Unavailable
Wikipedia: Florbetaben_F18
ChEMBL: CHEMBL1908906

On March 19th the FDA approved  Florbetaben F18 (Neuraceq™) as a radioactive diagnostic agent for Positron Emission Tomography (PET) imaging of the brain to estimate β-amyloid (βA) neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer’s disease or other causes of cognitive decline.

Alzheimer's disease is the most common form of dementia, can currently not be cured and is characterised by a progressive disease pattern that usually leads to death.  Alzheimer's is predicted to affect 1 in 85 people globally by 2050.

Target(s)
Florbetaben binds with high affinity to βA in brain homogenates and selectively labels βA plaques and cerebral amyloid angiopathy. βA (PDB ; Uniprot P05067) denotes 36-43 length peptides that are believed to be crucially involved in the Alzheimer's disease mechanism. βA aggregates in the brain of Alzheimer's patients and is derived from amyloid precursor protein which is cut by certain enzymes. βA and the resulting plaques are toxic to neurons. Following intravenous administration, Florbetaben F18 crosses the blood brain barrier and shows differential retention in brain regions that contain βA deposits. Differences in signal intensity between brain regions showing specific and non­ specific Florbetaben F18 uptake form the basis for the image interpretation method.



Florbetaben F18 (CHEMBL1908906Pubchem : 53257383) is a small molecule drug with a molecular weight of 359.4 Da, an AlogP of 3.75, 12 rotatable bonds, and no rule of 5 violations. Florbetaben F18 
is administered intravenously.

Canonical SMILES: CNc1ccc(\C=C\c2ccc(OCCOCCOCCF)cc2)cc1
InChi: InChI=1S/C21H26FNO3/c1-23-20-8-4-18(5-9-20)2-3-19-6-10-21(11-7-19)26-17-16-25-15-14-24-13-12-22/h2-11,23H,12-17H2,1H3/b3-2+

Dosage
The recommended dose of Neuraceq is 300 MBq (8.1 mCi), maximum 30 mcg mass dose, administered as a single
slow intravenous bolus (6 sec/mL) in a total volume of up to 10 mL. PET images should subsequently be acquired approximately 45 - 130 minutes after injection over a period of 15-20 minutes. 

Warning / limitations of use
A positive Neuraceq scan does not establish the diagnosis of AD or any other cognitive disorder.
Safety and effectiveness of Neuraceq have not been established for:
  • Predicting development of dementia or other neurologic conditions;
  • Monitoring responses to therapies.
Neuraceq, similar to other radiopharmaceuticals, contributes to a patient's overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk of cancer.

Pharmacokinetics
Ten minutes after intravenous bolus injection of 300 MBq of Neuraceq in human volunteers, approximately 6% of the injected radioactivity was distributed to the brain. Florbetaben F 18 plasma concentrations declined by approximately 75% at 20 minutes post-injection, and by approximately 90% at 50 minutes.

Elimination
Florbetaben F18 is mainly eliminated via the hepatobiliary route with a mean half-life of approximately 1 hour. 

Metabolism
Forbetaben F18 is metabolized mainly by CYP2J2 and CYP4F2.

License holder
The license holder is Piramal Imaging, the highlights of the prescribing information can be found here.

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