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Phase 3 Trial of Flutemetamol Labeled With Radioactive Fluorine 18 Imaging and Neuritic Plaque Density

2015; American Medical Association; Volume: 72; Issue: 3 Linguagem: Inglês

10.1001/jamaneurol.2014.4144

2168-6157

Craig Curtis, José E. Gámez, Upinder Singh, Carl Sadowsky, Teresa Villena, Marwan N. Sabbagh, Thomas G. Beach, Ranjan Duara, Adam Fleisher, Kirk A. Frey, Zuzana Walker, Arvinder Hunjan, Clive Holmes, Yavir M. Escovar, Carla X. Vera, Marc Agronin, Joel Ross, Andrea Bozoki, Mary Akinola, Jiong Shi, Rik Vandenberghe, Miloš D. Ikonomović, Paul Sherwin, Igor D. Grachev, Gillian Farrar, Adrian Smith, Christopher Buckley, Richard McLain, Stephen Salloway,

Medical Imaging Techniques and Applications

In vivo imaging of brain β-amyloid, a hallmark of Alzheimer disease, may assist in the clinical assessment of suspected Alzheimer disease. To determine the sensitivity and specificity of positron emission tomography imaging with flutemetamol injection labeled with radioactive fluorine 18 to detect β-amyloid in the brain using neuropathologically determined neuritic plaque levels as the standard of truth. Open-label multicenter imaging study that took place at dementia clinics, memory centers, and hospice centers in the United States and England from June 22, 2010, to November 23, 2011. Participants included terminally ill patients who were 55 years or older with a life expectancy of less than 1 year. Flutemetamol injection labeled with radioactive fluorine 18 (Vizamyl; GE Healthcare) administration followed by positron emission tomography imaging and subsequent brain donation. Sensitivity and specificity of flutemetamol injection labeled with radioactive fluorine 18 positron emission tomography imaging for brain β-amyloid. Images were reviewed without and with computed tomography scans and classified as positive or negative for β-amyloid by 5 readers who were blind to patient information. In patients who died, neuropathologically determined neuritic plaque levels were used to confirm scan interpretations and determine sensitivity and specificity. Of 176 patients with evaluable images, 68 patients (38%) died during the study, were autopsied, and had neuritic plaque levels determined; 25 brains (37%) were β-amyloid negative; and 43 brains (63%) were β-amyloid positive. Imaging was performed a mean of 3.5 months (range, 0 to 13 months) before death. Sensitivity without computed tomography was 81% to 93% (median, 88%). Median specificity was 88%, with 4 of 5 of the readers having specificity greater than 80%. When scans were interpreted with computed tomography images, sensitivity and specificity improved for most readers but the differences were not significant. The area under the receiver operating curve was 0.90. There were no clinically meaningful findings in safety parameters. This study showed that flutemetamol injection labeled with radioactive fluorine 18 was safe and had high sensitivity and specificity in an end-of-life population. In vivo detection of brain β-amyloid plaque density may increase diagnostic accuracy in cognitively impaired patients.