Drug information of Florbetapir F18

Florbetapir F18

Drug group:

Florbetapir (18F) is a radiopharmaceutical compound containing the radionuclide fluorine-18 bound to the compound florbetapir, a molecule that binds with high affinity to beta amyloid plaque, a peptide that plays a key role in Alzheimer's Disease pathogenesis. Marketed as the product Amyvid, florbetapir 18F 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) and other causes of cognitive decline.

The radionucleide fluorine-18 was chosen as it has a half life of 110 minutes allowing it to accumulate sufficiently in the brain before undergoing positon emission decay.

Mechanism of effect

Binds to beta-amyloid plaques and the F 18 isotope produces a positron signal that is detected by a PET scanner

In in vitro binding studies using postmortem human brain homogenates containing beta-amyloid plaques, the dissociation constant (Kd) for florbetapir was 3.7± 0.3 nM

Pharmacodynamic

Following intravenous injection, florbetapir F 18 diffuses across the human blood-brain barrier and produces a radioactivity signal detectable throughout the brain. Subsequently, cerebral perfusion decreases the brain florbetapir F 18 content, with differential retention of the drug in areas that contain β-amyloid aggregates compared to areas that lack the aggregates.

Pharmacokinetics

absorbtion
The time-activity curves for florbetapir F 18 in the brain of subjects with positive scans show continual signal increases from time zero through 30 minutes post-administration, with stable values thereafter up to at least 90 minutes post-injection. Following the intravenous administration of 370 MBq (10 mCi) of florbetapir F 18 to healthy volunteers, the drug was distributed throughout the body with less than 5% of the injected F 18 radioactivity present in the blood by 20 minutes following administration, and less than 2% present by 45 minutes after administration

Distribution

Rapidly distributed throughout body

<5% of the injected F 18 radioactivity present in the blood by 20 minutes following administration, and less than 2% present by 45 minutes after administration
Metabolism

The residual F 18 in circulation during the 30-90 minute imaging window was principally in the form of polar F 18 metabolites. Essentially all radioactivity collected in the urine was present as polar metabolites of florbetapir F 18. Three metabolites have been discovered and identified as [18F]AV-160 (desmethyl-[18F]AV-45), [18F]AV-267 (N-acetyl–[18F]AV-160), and an [18F]-Polar species, the identity of which has not been confirmed. Additionally, although metabolites may make some contribution to signal detection, particularly to the nontarget activity, it is concluded that there will be minimal interference from these radiolabeled metabolites to the amyloid target binding in the [18F]AV-45 brain PET image

Elimination

Half-life: 109.77 minutes (F 18)

Excretion: Principally via feces (GI and bile), small amount in urine

 

Drug indications

Diagnostic imaging

Dosage

  • 370 MBq (10 mCi) as a single IV bolus injection in a total volume of 10 mL or less; follow bolus injection 0.9% NaCl IV flush
  • Not to exceed 50 mcg mass dose
  • Inject through a short IV catheter (~1.5 inches or less) to minimize the potential for adsorption of the drug to the catheter

Limitations of use

  • Positive scan does not establish a diagnosis of AD or other cognitive disorder
  • Safety and effectiveness have not been established for: 1) predicting development of dementia or other neurologic condition; 2) monitoring responses to therapies

Image Display & Interpretation

A 10-minute PET image should be acquired starting 30-50 minutes after IV injection

The patient should be supine; position head to center the brain, including the cerebellum, in the PET scanner field of view

Reduce head movement with tape or other flexible head restraints may be employed

Image reconstruction should include attenuation correction with resulting transaxial pixel sizes between 2 and 3 mm

Alerts

Risk for image misinterpretation

  • Errors may occur in the estimation of brain neuritic plaque density during image interpretation; perform image interpretation independently of the patient’s clinical information
  • Other errors may be due to extensive brain atrophy that limits the ability to distinguish gray and white matter on the scan as well as motion artifacts that distort the image

Radiation risk

  • Similar to other radiopharmaceuticals, florbetapir F 18 contributes to a patient’s overall long-term cumulative radiation exposure; long-term cumulative radiation exposure is associated with an increased risk of cancer
  • Ensure safe handling to protect patients and health care workers from unintentional radiation exposure

Points of recommendation

IV Preparation

Must not be diluted

Inspect the radiopharmaceutical dose solution prior to administration and do not use it if it contains particulate matter or is discolored

Use aseptic technique and radiation shielding to withdraw solution

Assay the dose in a suitable dose calibrator prior to administration

Radiation safety

  • Radioactive drug; handle with appropriate safety measures to minimize radiation exposure during administration
  • Use waterproof gloves and effective shielding, including lead-glass syringe shields when handling
  • Radiopharmaceuticals should only be used by or under the control of physicians who are qualified by specific training and experience in the safe use and handling of radioactive materials, and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radiopharmaceuticals

IV Administration

Inject through a short IV catheter (~1.5 inches or less) to minimize the potential for adsorption of the drug to the catheter

Portions of the dose may adhere to longer catheters

Administer as single IV bolus injection in a total volume of 10 mL or less; follow bolus injection 0.9% NaCl IV flush

Not to exceed 50 mcg mass dose

Storage

Store at 25ºC (77°F); excursions permitted to 15-30ºC (59-86°F)

The product does not contain a preservative

Store within the original container or equivalent radiation shielding

This preparation is approved for use by persons under license by the Nuclear Regulatory Commission or the relevant regulatory authority of an Agreement State

Pregnancy level

HAVE NOT BEEN ESTABLISHED

There are no available data on use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

All radiopharmaceuticals, have potential to cause fetal harm depending on stage of fetal development, and magnitude of radiopharmaceutical dose

If considering administration to a pregnant woman, inform patient about potential for adverse pregnancy outcomes based on radiation dose from drug and gestational timing of exposure

Breast feeding warning

There are no data on presence of drug or metabolites in human milk or effects on breastfed infant or milk production

Exposure to a breastfed infant can be minimized by temporary discontinuation of breastfeeding

The developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal condition

To decrease radiation exposure to breastfed infant, advise a lactating woman to interrupt breastfeeding, and pump and discard breast milk for 24 hours after administration of drug

Drug forms

AMYViD

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