Quantitative Evaluation of 18F-Flutemetamol PET in Patients With Cognitive Impairment and Suspected Alzheimer's Disease: A Multicenter Study

Frontiers in Neurology

Sunao Mizumura¹  Miyako Morooka¹  Kenji Ishibashi²  Kenji Ishii²  Takashi Kato³  Akinori Takenaka³  Kohei Hanaoka⁴  Jun Hatazawa⁴  Masamichi Ikawa⁵  Masashi Kameyama⁶  Tensho Yamao⁷  Kenta Miwa⁷  Hidehiko Okazawa⁸  Tetsuya Tsujikawa⁸  Hiroshi Matsuda⁹  Yoko Shigemoto⁹  Eku Shimosegawa^1,10  Keiko Matsunaga^1,10  Masahiro Mishina^1,11  Noriko Sato^1,13  Hayato Kaida^1,14  Kazunari Ishii^1,14  Kengo Ito^1,15  Kyoji Okita^1,16  Masayo Ogawa^1,16 

[1] 0Department of Radiology, Medical Centre Omori, Toho University, Tokyo, Japan;1Team for Neuroimaging Research, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan;2Department of Radiology, National Center for Geriatrics and Gerontology, Obu, Japan;3Joint Research Division for the Quantum Cancer Therapy, Research Center for Nuclear Physics, Osaka University, Osaka, Japan;4Department of Neurology, Faculty of Medical Sciences, Fukui, Japan;5Department of Radiology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan;6Preparing Section for New Faculty of Medical Science, Fukushima Medical University, Fukushima, Japan;Biomedical Imaging Research Center, University of Fukui, Fukui, Japan;Cyclotron and Drug Discovery Research Center, Southern TOHOKU Research Institute for Neuroscience, Koriyama, Japan;Department of Molecular Imaging in Medicine, Osaka University Graduate School of Medicine, Suita, Japan;Department of Neuro-Pathophysiological Imaging, Graduate School of Medicine, Nippon Medical School, Kawasaki, Japan;Department of Radiology, Kindai University Faculty of Medicine, Osakasayama, Japan;Department of Radiology, National Center of Neurology and Psychiatry, Kodaira, Japan;Division of Positron Emission Tomography, Institute of Advanced Clinical Medicine, Kindai University Hospital, Osakasayama, Japan;Innovation Center for Clinical Research, National Center for Geriatrics and Gerontology, Obu, Japan;Integrative Brain Imaging Center, National Center of Neurology and Psychiatry, Kodaira, Japan;

关键词: amyloid imaging;    positron emission tomography;    Alzheimer's disease;    18F-flutemetamol;    standardized uptake value ratio;    centiloid scale;   

DOI  :  10.3389/fneur.2020.578753

来源: DOAJ

【 摘 要 】

Background: In clinical practice, equivocal findings are inevitable in visual interpretation of whether amyloid positron emission tomography (PET) is positive or negative. It is therefore necessary to establish a more objective quantitative evaluation method for determining the indication for disease-modifying drugs currently under development.Aims: We aimed to determine cutoffs for positivity in quantitative analysis of 18F-flutemetamol PET in patients with cognitive impairment and suspected Alzheimer's disease (AD). We also evaluated the clinical efficacy of amyloid PET in the diagnosis of AD. This study was registered in the Japan Registry of Clinical Trials (jRCTs, 031180321).Methods: Ninety-three patients suspected of having AD underwent 18F-flutemetamol PET in seven institutions. A PET image for each patient was visually assessed and dichotomously rated as either amyloid-positive or amyloid-negative by two board-certified nuclear medicine physicians. If the two readers obtained different interpretations, the visual rating was rerun until they reached consensus. The PET images were quantitatively analyzed using the standardized uptake value ratio (SUVR) and standardized Centiloid (CL) scale with the whole cerebellum as a reference area.Results: Visual interpretation obtained 61 positive and 32 negative PET scans. Receiver operating characteristic analysis determined the best agreement of quantitative assessments and visual interpretation of PET scans to have an area under curve of 0.982 at an SUVR of 1.13 and a CL of 16. Using these cutoff values, there was high agreement between the two approaches (kappa = 0.88). Five discordant cases had SUVR and CL values ranging from 1.00 to 1.22 and from 1 to 26, respectively. In these discordant cases, either diffuse or mildly focal elevation of cortical activity confused visual interpretation. The amyloid PET outcome significantly altered the diagnosis of AD (χ2 = 51.3, p < 0.0001). PET imaging elevated the proportions of the very high likelihood category from 20.4 to 46.2% and the very low likelihood category from 0 to 22.6%.Conclusion: Quantitative analysis of amyloid PET using 18F-flutemetamol can objectively evaluate amyloid positivity using the determined cutoffs for SUVR and CL. Moreover, amyloid PET may have added value over the standard diagnostic workup in dementia patients with cognitive impairment and suspected AD.

【 授权许可】

Unknown