New study data presented at the Alzheimer's Association International Conference® 2014 (AAIC®) showed that a positive [18F]flutemetamol PET scan for brain amyloid was a highly significant predictor of progression from amnestic Mild Cognitive Impairment (aMCI) to probable Alzheimer's disease (pAD).[i] A second study further demonstrated the diagnostic value of [18F]flutemetamol in confirming the presence of neuritic amyloid in those patients with early onset dementia.[ii] [18F]Flutemetamol is GE Healthcare's investigational radiopharmaceutical product for PET imaging of beta amyloid neuritic plaque density in the brains of adult patients with cognitive impairment who are being evaluated for Alzheimer's disease and other causes of cognitive impairment.
"Collectively, these data demonstrate the diagnostic value of [18F]flutemetamol and add to the growing body of evidence that it can help physicians identify the histopathology associated with an Alzheimer's disease diagnosis in specific patients," said Ger Brophy, PhD, Chief Technology Officer, Life Sciences, GE Healthcare. "If and when approved in the European Union, [18F]flutemetamol will be an important tool to support assessments of patients with cognitive disorders, as well as being a valuable research tool in the hunt for therapies to combat Alzheimer's."
Use of [18F]Flutemetamol PET Scans as Indicator of Progression from Amnestic Mild Cognitive Impairment to Probable Alzheimer's Disease
In the study, 232 participants with MCI, a diagnosis characterized by cognitive deficits not severe enough to impact daily functioning and thus not meeting the definition of dementia, received a [18F]flutemetamol injection and underwent brain scans. The study showed those with positive VIZAMYL scans were approximately 2.5 times more likely to convert to pAD than those with negative scans. The ability of positive [18F]flutemetamol PET images to identify aMCI patients at higher risk of progressing to AD could potentially allow for better patient evaluation and management, and support patient stratification in enrolment into clinical trials for disease modifying drugs
"These findings demonstrate the potential role of [18F]flutemetamol in stratifying those patients at higher risk of developing Alzheimer's disease, beyond its use as a diagnostic tool," said David Wolk, MD, Assistant Director, Penn Memory Center and Lead Investigator of the study. "In addition to providing patients with potentially important prognostic information about their likelihood of developing dementia, identifying high risk patients could help guide physicians' recommendations for patient monitoring, care plans and use diagnostic resources. These are exciting results, but we need further research to fully understand how this might be used in clinical practice."
Diagnostic Value of [18F]Flutemetamol) in Early Onset Dementia
In this study, 80 patients with early onset dementia (younger than age 70), and with physician diagnostic confidence less than 90 percent, underwent [18F]flutemetamol PET scans which were assessed as either amyloid positive or negative. Clinical diagnosis and diagnostic confidence was determined, both before and after disclosure of the scan results. This study demonstrated that the use of [18F]flutemetamol increased diagnostic confidence for physicians, and in many patients, helped to confirm or exclude the diagnosis of Alzheimer's disease and lead to changes in management.
"Early and accurate diagnoses may have implications for both prognosis and treatment among patients with early onset dementia," said Dr. Marissa Zwan, VU University Medical Center, Amsterdam and Lead Investigator of the study. "Greater diagnostic confidence supports better patient management and helps physicians to determine appropriate treatment options, as well as helping patients and caregivers to plan for the future."
The data showed that 20 percent of patients had a change in diagnosis following review of the [18F]flutemetamol scan. In particular, for those patients diagnosed with Alzheimer's disease prior to a [18F]flutemetamol scan and who had an amyloid negative result, clinical diagnosis changed in 12 of 15 patients. Overall, confidence in diagnosis significantly increased from 67(±12) percent to 90(±16) percent after disclosing PET results. Additionally, in 48 percent of patients, [18F]flutemetamol PET results led to a change in patient healthcare management (i.e. medication changes, additional care).
In October 2013, [18F]flutemetamol received approval from the U.S. Food and Drug Administration, where it is marketed as VIZAMYL™, for Positron Emission Tomography (PET) imaging of the brain to estimate beta amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer's disease (AD) or other causes of cognitive decline. VIZAMYL is for diagnostic use only and should be used in conjunction with a clinical evaluation. VIZAMYL is not licensed in any market for estimating the risk of MCI progression to clinical AD.
In June 2014, [18F]flutemetamol received a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP), recommending the granting of a marketing authorization for PET imaging of beta amyloid neuritic plaque density in the brains of adult patients with cognitive impairment who are being evaluated for Alzheimer's disease and other causes of cognitive impairment. It is not yet approved for use in Europe or Japan.