Craig Curtis1, Jose E Gamez2, Upinder Singh3, Carl H Sadowsky4, Teresa Villena5, Marwan N Sabbagh6, Thomas G Beach6, Ranjan Duara7, Adam S Fleisher8, Kirk A Frey9, Zuzana Walker10, Arvinder Hunjan11, Clive Holmes12, Yavir M Escovar13, Carla X Vera13, Marc E Agronin14, Joel Ross15, Andrea Bozoki16, Mary Akinola17, Jiong Shi18, Rik Vandenberghe19, Milos D Ikonomovic20, Paul F Sherwin21, Igor D Grachev22, Gillian Farrar23, Adrian P L Smith23, Christopher J Buckley23, Richard McLain24, Stephen Salloway25. 1. Compass Research, Orlando, Florida. 2. Galiz Research, Miami Springs, Florida. 3. Geriatric Solutions, Las Vegas, Nevada. 4. Department of Neurology, Nova SE University, Ft Lauderdale, Florida. 5. Premiere Research Institute, West Palm Beach, Florida. 6. Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, Arizona. 7. Mount Sinai Medical Center, Wien Center for AD, Miami Beach, Florida. 8. Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, Arizona8is now with Eli Lilly and Company, Indianapolis, Indiana9is now with the Department of Neurosciences, University of California, San Diego, San Diego. 9. Department of Radiology, Nuclear Medicine, University of Michigan, Ann Arbor. 10. Division of Psychiatry, University College London, England12North Essex Partnership University NHS Foundation Trust, London, England. 11. North Essex Partnership University NHS Foundation Trust, Essex, England. 12. Clinical Experimental Science, University of Southampton, Southampton, Hampshire, England. 13. VERITAS Research, Miami Lakes, Florida. 14. Mental Health and Clinical Research, Miami Jewish Health Systems, Miami, Florida17Department of Psychiatry and Neurology, University of Miami Miller School of Medicine, Miami, Florida. 15. Memory Enhancement Center, Eatontown, New Jersey. 16. Cognitive and Geriatric Neurology Team, Neurology and Radiology, Michigan State University, East Lansing. 17. Kennington Health Centre, Oxford, England. 18. Department of Neurology, Barrow Neurological Institute, Phoenix, Arizona. 19. Department of Neurology, University Hospitals Leuven, Leuven, Belgium. 20. Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania. 21. Medical Affairs, GE Healthcare-Life Sciences, Princeton, New Jersey. 22. Medical Affairs, GE Healthcare-Life Sciences, Princeton, New Jersey25is now with Novartis Consumer Health, Parsippany, New Jersey26is now with Genpact Pharmalink, Short Hills, New Jersey. 23. Life Sciences, GE Healthcare, Amersham, Buckinghamshire, England. 24. PFP Statistical Consulting LLC, Livonia, Michigan. 25. Department of Neurology and the Memory and Aging Program, Butler Hospital, Providence, Rhode Island30Department of Neurology and Psychiatry, Warren Alpert Medical School, Providence, Rhode Island31Brown University, Providence, Rhode Island.
Abstract
IMPORTANCE: In vivo imaging of brain β-amyloid, a hallmark of Alzheimer disease, may assist in the clinical assessment of suspected Alzheimer disease. OBJECTIVE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: Flutemetamol injection labeled with radioactive fluorine 18 (Vizamyl; GE Healthcare) administration followed by positron emission tomography imaging and subsequent brain donation. MAIN OUTCOMES AND MEASURES: 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. RESULTS: 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. CONCLUSIONS AND RELEVANCE: 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.
IMPORTANCE: In vivo imaging of brain β-amyloid, a hallmark of Alzheimer disease, may assist in the clinical assessment of suspected Alzheimer disease. OBJECTIVE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS:Flutemetamol injection labeled with radioactive fluorine 18 (Vizamyl; GE Healthcare) administration followed by positron emission tomography imaging and subsequent brain donation. MAIN OUTCOMES AND MEASURES: 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. RESULTS: 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. CONCLUSIONS AND RELEVANCE: 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 impairedpatients.
Authors: Erik Portelius; Henrik Zetterberg; Tobias Skillbäck; Ulrika Törnqvist; Ulf Andreasson; John Q Trojanowski; Michael W Weiner; Leslie M Shaw; Niklas Mattsson; Kaj Blennow Journal: Brain Date: 2015-09-15 Impact factor: 13.501
Authors: Eric E Abrahamson; Elizabeth Head; Ira T Lott; Benjamin L Handen; Elliott J Mufson; Bradley T Christian; William E Klunk; Milos D Ikonomovic Journal: Dev Neurobiol Date: 2019-08-17 Impact factor: 3.964
Authors: Michael J Pontecorvo; Anupa K Arora; Marybeth Devine; Ming Lu; Nick Galante; Andrew Siderowf; Catherine Devadanam; Abhinay D Joshi; Stephen L Heun; Brian F Teske; Stephen P Truocchio; Michael Krautkramer; Michael D Devous; Mark A Mintun Journal: Eur J Nucl Med Mol Imaging Date: 2017-01-07 Impact factor: 9.236