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Florbetapir

Clinical data
Trade names	Amyvid
Routes of administration	Intravenous
Legal status
Legal status	US: ℞-only
Identifiers
IUPAC name (E)-4-(2-(6-(2-(2-(2[18F] fluoroethoxy)ethoxy)ethoxy)pyridine-3-yl)vinyl)-N-methylbenzamine
PubChem CID	24822371
Chemical and physical data
Formula	C14H22N2O2
Molar mass	250.33668 [g/mol] g·mol−1

Florbetapir

Florbetapir is a drug used to image plaques in the brain pertaining to Alzheimer’s disease. As the prevalence of Alzheimer’s disease increases, such a drug plays a large role in learning more about the disease including its initiation, diagnosis, and progression. The introduction of florbetapir as an imaging agent allows doctors to be able to see Alzheimer’s sooner in the progression than previously possible. In the imaging of Amyvid in the brain, a PET scan provides a 3D image of the brain with the varying densities pictured.

History

Florbetapir is produced by Lilly under the name Amyvid. Amyvid was the first radioactive agent approved by the FDA for imaging beta amyloid plaques in the living brain, with approval announced April 10, 2012. Lilly has been in the race for development of an imaging tool of Alzheimer's for years, with the approval of Amyvid possibly leading it to its global market potential of 1 to 5 billion dollars.

Mechanism

Florbetapir diffuses across the blood-brain barrier in order to bind to aggregates in the brain. The isotope in florbetapir, 18F, produces a signal that can be analyzed by a PET scanner.

Indications

Florbetapir, or Amyvid, is used to assess the density of the beta amyloid plaque in the brain. Amyvid is indicated for use in adults with cognitive impairment who are being evaluated for Alzheimer’s or other causes for cognitive decline. Amyvid is not to be used on children.

Administration

Amyvid is administered intravenously, followed by an injection of sodium chloride in order to flush the Amyvid through completely. The drug is radioactive, as it marks the brain with an isotope of fluorine, making minimization of radiation exposure mandatory during administration for both the patient and the healthcare provider. A 10 minute PET image is acquired approximately 30 to 50 minutes after the injection.

Scan Results

In the PET scans, the positive signs for β-amyloid plaques being present are scans showing a loss in grey matter. In addition, tracts are hard to visualize and distinctions in regions of the brain that are typically seen are no longer evident. A positive scan indicates that there is a moderate amount of plaques shown in the image. A positive scan, however, does not permit a diagnosis of Alzheimer’s, as high amounts of plaques are also seen in patients with other conditions and older patients with normal cognition.A negative scan shows few or no plaques in the brain and indicates that the cognitive impairment is not due to Alzheimer’s disease.

Images are only interpreted by physicians who have completed the training program. Only estimates can be determined from the scans, not diagnoses. Reading images is solely based on image features and not characteristics of the patient. Positive or negative results are determined by comparing white matter and grey matter. Radioactivity in the white matter is normal, but when there is little to no contrast between the white and grey matter, plaques are evident.

Risks and Side Effects

Side effects and adverse reactions seen in clinical studies included headache, fatigue, nausea, anxiety, claustrophobia, neck pain, back pain, and others. None of the side effects were experienced by a large percentage of the study groups. Most commonly, headaches resulted, with 1.8% of the patients. The remainder of the side effects were noted by fewer than 1% of the patients. It is unknown whether the drug has any negative effects for pregnancies or nursing mothers. Amyvid is not indicated for the pediatric population. Most common administration is to the geriatric population, as they are most often diagnosed with Alzheimer’s and cognitive decline. Drug interactions have not yet been studied. It is unknown if there are drugs that interfere with the scan results. Another risk involved in the use of Amyvid is error in the estimation of the plaque density. Motion artifacts can distort the scan. In the training for reading the scans of Amyvid, it is recommended that the image interpretation should be done without knowledge of a patient’s clinical information as knowing the history of the patient may lead to errors in reading of the scans.

In the News

Popular opinion of Amyvid varies due to the inability to actually diagnose Alzheimer’s with scan results. However, the drug is a huge step in the right direction for diagnosis. The director of the FDA, Janet Woodcock, stated,

“Until now, the brain content of β-amyloid neuritic plaques could only be determined with a brain biopsy or examination of the brain at autopsy. This imaging agent is one tool to help physicians in the assessment of their patients by serving as an adjunct to other diagnostic evaluations.”

R. Edward Coleman, M.D., also stated,

“this approval marks a great advancement in nuclear medicine practice, as it enables us to evaluate the presence or absence of moderate to frequent levels of amyloid plaques in a patient’s brain.”

Opinions of the drug are generally positive when used in conjunction with other diagnosing tools. General agreement is that the test, though it cannot give a diagnosis, it can be used as a viable tool when diagnosing Alzheimer’s earlier.