Just-Published Analysis Exposes Serious Problems in Experimental Procedure for Diagnosing Alzheimer’s Disease

Oct. 21, 2011  

Just-Published Analysis Exposes Serious Problems in Experimental Procedure for Diagnosing Alzheimer’s Disease

Statement of Dr. Michael Carome, Deputy Director, Public Citizen’s Health Research Group

Experts on neuroimagingtechniques for the detection and evaluation of dementia published an editorial online this week in the European Journal of Nuclear Medicine and Molecular Imaging highlighting serious problems with a type of brain scan using an experimental dye for detecting brain abnormalities found in patients with Alzheimer’s disease.

Alzheimer’s disease is the leading cause of irreversible dementia in the United States. Currently, there is no definitive test for diagnosing Alzheimer’s disease while a patient is alive, so the diagnosis typically is made by doing tests to exclude other causes of dementia, such as strokes, certain nutritional deficiencies and hypothyroidism. Autopsy studies looking at the brains of Alzheimer’s disease patients have revealed plaques (deposits) of an abnormal protein called beta-amyloid, but not all individuals with beta-amyloid plaques in their brains had dementia. 

Avid Pharmaceuticals, the company that developed the experimental dye – called florbetapir F 18 – is seeking approval from the U.S. Food and Drug Administration (FDA) to market the dye for the purpose of detecting beta-amyloid plaques in the brains of living people using an imaging procedure called a positron emission tomography (PET) scan.

However, in their just-published editorial, senior author Dr. Abass Alavi and his colleagues identified numerous troubling aspects of florbetapir-PET imaging that undermine any support for the claim that florbetapir-PET scanning is useful for imaging of beta-amyloid aggregates in the brain, including the following:

  • Imaging studies conducted with florbetapir, as well as virtually any other proposed beta-amyloid dye, consistently have shown the frontal lobes of the brain to have one of – if not the – highest signal for florbetapir uptake. In contrast, autopsy studies of brain from Alzheimer’s disease patients, the gold-standard procedure for detecting beta-amyloid, have shown that the highest density of beta-amyloid deposits was found in the temporal and occipital lobes, whereas the lowest concentration was seen in the limbic and frontal lobes.
  • PET imaging with amyloid agents such as florbetapir shows substantial uptake in white matter of the brain, whereas beta-amyloid deposits are found in grey matter, with little if any in white matter.
  • Given the size of beta-amyloid plaques and the small percentage of total brain area occupied by beta-amyloid plaques even in the most severely affected regions of the brain, amyloid agents such as florbetapir almost certainly do not have sufficiently greater uptake in beta-amyloid deposits than in the background to allow accurate detection of beta-amyloid deposits on PET imaging.

Thus, florbetapir-PET scans in studies with human subjects have shown the strongest positive results in those parts of the brain that should have the least or no beta-amyloid deposits. Such results indicate that florbetapir is not useful for detecting beta-amyloid deposits in the brain.

In a Feb. 21, 2011, letter to the FDA, as well as a recently published letter to the editor of the Journal of the American Medical Association, we urged the FDA not to approve florbetapir-PET imaging because of studies showing a lack of consistency in reading florbetapir-PET scans from one radiologist to the next. Given such inter-reader variability, such PET scans would have little clinical utility in the evaluation of patients presenting with cognitive deficits or early dementia and suspected of having Alzheimer’s disease.

   In another letter submitted to the FDA today, Public Citizen submitted a copy of editorial written by Dr. Alavi and his colleagues and again called upon the FDA to reject approval of florbetapir.

To see Public Citizen’s letters to the FDA regarding florbetapir, visit: https://www.citizen.org/our-work/health-and-safety/articles/letter-fda-urging-rejection-florbetapir-f18-injection-amyvidand https://www.citizen.org/our-work/health-and-safety/articles/letter-encouraging-rejection-florbetapir-f18-injection-amyvid.

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