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PET scans using radio-labeled flutemetamol were safe to use in vivo and confirmed the presence or absence of neuritic beta-amyloid levels “with high sensitivity and specificity” in a phase III trial involving 68 terminally ill older adults.
“In-vivo detection of brain beta-amyloid may help increase diagnostic accuracy in cognitively impaired patients, compared with clinical diagnosis alone,” wrote Dr. Craig Curtis of Compass Research, Orlando, and his associates in their report (JAMA Neurol. 2015;72:287-94).
The PET scanning agent used in the study, [18F]flutemetamol (Vizamyl), binds with high affinity to beta-amyloid but rapidly clears from normal brain tissue; it was approved in October 2013 for PET imaging of the brain in adults being evaluated for Alzheimer’s disease and dementia.
The trial involved 203 consecutive patients attending 19 dementia clinics, memory centers, and hospices in the United States and England who were aged 55 years and older and who had a life expectancy of 1 year or less. A total of 180 who underwent [18F]flutemetamol PET scanning comprised the population for the safety analysis. A subset of 68 patients who died during the study period underwent autopsy so that brain pathology could be compared with the PET images; these patients comprised the sensitivity/specificity analysis.
Five specially trained readers who were blinded to patient information – four nuclear medicine physicians and one radiologist – independently interpreted the PET scans as being either positive or negative for neuritic beta-amyloid. All the images were of good technical quality, and none were considered unevaluable.
On postmortem examination, 25 of the 68 brains (37%) were found to be beta-amyloid negative and 43 (63%) to be beta-amyloid positive.
The sensitivity of [18F]flutemetamol PET scanning ranged from 81% to 93% (median, 88%) across the five scan readers, and the specificity ranged from 44% to 92% (median, 88%). One of the readers frequently overestimated the level of beta-amyloid in the scans and was considered an outlier regarding specificity. Between-reader agreement was 90% or higher when that reader’s interpretations were excluded from the analysis, the investigators said.
Overall, 6 (14%) of 43 brains found to be beta-amyloid positive at autopsy were read as false negatives, and 2 (8%) of 25 brains found to be beta-amyloid–negative at autopsy were read as false positives.
The intravenous [18F]flutemetamol injections were well tolerated, and no adverse events were attributed to the agent or the PET procedure. However, four participants were withdrawn from the study because they were unable to remain motionless in the scanner.
This study was funded by GE Healthcare, maker of [18F]flutemetamol, which also planned and conducted the data analysis. Dr. Curtis reported having no financial disclosures; his associates reported numerous ties to industry sources.