Dyeing to Paint the Alzheimer’s Brain
News Apr 12, 2012
The three hallmark biomarkers for AD are neurofibrillary “tangles”, protein amyloid or “neuritic plaques”, and granulovacuolar degeneration of neurons. Unfortunately there is currently no “live” brain imaging diagnostic tool per se, as the imaging which is used occurs only when the progression of the disease is late-stage or postmortem.
Computed tomography (CT) and magnetic resonance imaging (MRI) have been used for years to rule out other causes of dementia. More recently, positron emission tomography (PET) and cerebral metabolism using fluoro-deoxy-D-glucose (FDG) have been used to show characteristic changes in the brain and help rule-in Alzheimer’s pathophysiological processes.
On April 9, 2012, the FDA approved Avid Radiopharmaceuticals’ (now part of Eli Lilly) Amyvid which is a brain plaque diagnostic tool using florbetapir (F-AV-45). This radiotracer dye agent is delivered intravenously and is drawn to beta-amyloid, thus allowing a physician to see accumulations of amyloid in the brain. These accumulations can help physicians to determine whether a patient is suffering from some form of dementia, but cannot confirm a diagnosis of AD. Several other diseases such as Parkinson’s disease, Huntington’s disease, and Creutzfeldt-Jakob disease characteristically present with plaques as well, therefore physicians must still use mental and behavior cues to diagnose a patient with AD.
Amyvid has the benefit that its half-life is close to 110 minutes, compared to the previously used radiotracer known as PiB (Pittsburg compound B [fluorescent analog of thioflavin T]) which offered a half-life of only 20 minutes. A longer half-life means more time allowed for the physicians to perform the injection and analysis of a patient. Unfortunately, the downside to using florbetapir is its high cost and patient exposure to radioactive material.
Amyvid is the only FDA-approved diagnostic PET tracer for imaging plaques in vivo, but there looks to be another agent in the pipeline that could potentially provide more diagnostic armament for detecting Alzheimer’s disease. Navidea Biopharmaceuticals’ AZD4694 Fluorine-18 labeled dye has completed Phase IIa clinical trials, and Phase III clinical trials will likely begin in 2013. This entity has been shown to be highly sensitive in detecting amyloid plaque, therefore signal to noise ratio remains low due to low background and white matter uptake; thus providing clear images of amyloid plaques. Navidea hopes AZD4694 will be used as an early identification tool for Alzheimer’s disease.
The next step for brain imaging will have to be an imaging agent which can lead to an Alzheimer’s disease diagnosis, but for now Amyvid will be a great complement for tracking disease progression. GlobalData is confident that with Amyvid on the market, more novel agents will follow to become primary diagnostic tools for the diagnosis of Alzheimer’s disease.
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