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Annals of Nuclear Medicine
Published in: Annals of Nuclear Medicine 7/2015

01-08-2015 | Original Article

Imaging characteristics and safety of florbetapir (18F) in Japanese healthy volunteers, patients with mild cognitive impairment and patients with Alzheimer’s disease

Authors: Chihiro Namiki, Yasushi Takita, Atsushi Iwata, Toshimitsu Momose, Michio Senda, Yoshiro Okubo, Abhinay D. Joshi, Ming Lu, Abigail Agbulos, Christopher Breault, Michael J. Pontecorvo

Published in: Annals of Nuclear Medicine | Issue 7/2015

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Abstract

Objective

The purpose of this study was to evaluate the performance characteristics and safety of florbetapir (I8F) positron emission tomography (PET) in patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI) and cognitively normal (CN) control patients from Japan.

Methods

Florbetapir (I8F) PET was obtained in 48 subjects (15 AD patients, 15 MCI patients, and 18 CNs) within a multicenter phase 2/3 study. Amyloid burden was assessed visually and classified as positive or negative for pathologic levels of amyloid aggregation, blind to diagnostic classification. Cerebral to cerebellar standardized uptake value ratios (SUVRs) were determined from the florbetapir (I8F) PET images. Safety was assessed by monitoring adverse events, vital signs, clinical laboratory assessments, and electrocardiograms. Demographic variables and cognitive scales were summarized by using descriptive statistics for each group. Fisher’s exact test and one-way analysis of variance were used to compare amyloid positivity and mean SUVRs, respectively, between diagnostic groups.

Results

Florbetapir (I8F) PET was rated visually amyloid positive in 80.0 % of AD patients, 33.3 % of MCI patients, and 16.7 % of CNs. Mean SUVRs were highest in the AD group and lowest in the CN group for each brain region (P < 0.01) and globally (P < 0.05). Kappa statistics showed strong inter-reader agreement (Fleiss’ kappa = 0.82) and individual reader’s agreement with the majority of readers (kappa ranged from 0.79 to 1.0). Seventeen of the 48 subjects (35.4 %) were Apolipoprotein E genotype ε4 positive, which included 10 subjects in the AD group and 7 subjects in the MCI group. A total of 6 subjects (5 of whom were in the CN group) had at least 1 treatment-emergent adverse event (TEAE).

Conclusions

These data indicate that amyloid positivity increased with diagnostic category (CN < MCI < AD) and are consistent with expected rates of amyloid positivity among individuals with clinical diagnoses of AD and MCI. In addition, these results were similar to those obtained in United States studies. Florbetapir (18F) was safe and well tolerated. The reliability of both qualitative and quantitative assessments of florbetapir (18F) in this study population provides support for potential use in clinical settings in Japan.
Literature
1.
Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, et al. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005;366(9503):2112–7.PubMedCentralPubMedCrossRef
2.
Anderson GF, Hussey PS. Population aging: a comparison among industrialized countries. Health Aff (Millwood). 2000;19(3):191–203.CrossRef
3.
Asada T. Prevalence of dementia in Japan: past, present and future. Rinsho Shinkeigaku. 2012;52(11):962–4.PubMedCrossRef
4.
5.
Knopman DS, DeKosky ST, Cummings JL, Chui H, Corey-Bloom J, Relkin N, et al. Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001;56(9):1143–53.PubMedCrossRef
6.
Consensus recommendations for the postmortem diagnosis of Alzheimer’s disease. The National Institute on Aging, and Reagan Institute Working Group on diagnostic criteria for the neuropathological assessment of Alzheimer’s disease. Neurobiol Aging. 1997;18(4 Suppl):S1–S2.
7.
Rowe CC, Villemagne VL. Amyloid imaging with PET in early Alzheimer disease diagnosis. Med Clin N Am. 2013;97(3):377–98.PubMedCrossRef
8.
Vandenberghe R, Adamczuk K, Dupont P, Laere KV, Chetelat G. Amyloid PET in clinical practice: its place in the multidimensional space of Alzheimer’s disease. Neuroimage Clin. 2013;2:497–511.PubMedCentralPubMedCrossRef
9.
Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh compound-B. Ann Neurol. 2004;55(3):306–19.PubMedCrossRef
10.
Nordberg A. Amyloid imaging in early detection of Alzheimer’s disease. Neurodegener Dis. 2010;7(1–3):136–8.PubMedCrossRef
11.
Koole M, Lewis DM, Buckley C, Nelissen N, Vandenbulcke M, Brooks DJ, et al. Whole-body biodistribution and radiation dosimetry of 18F-GE067: a radioligand for in vivo brain amyloid imaging. J Nucl Med. 2009;50(5):818–22.PubMedCrossRef
12.
Rowe CC, Ackerman U, Browne W, Mulligan R, Pike KL, O’Keefe G, et al. Imaging of amyloid beta in Alzheimer’s disease with 18F-BAY94-9172, a novel PET tracer: proof of mechanism. Lancet Neurol. 2008;7(2):129–35.PubMedCrossRef
13.
Small GW, Kepe V, Ercoli LM, Siddarth P, Bookheimer SY, Miller KJ, et al. PET of brain amyloid and tau in mild cognitive impairment. N Engl J Med. 2006;355(25):2652–63.PubMedCrossRef
14.
Choi SR, Golding G, Zhuang Z, Zhang W, Lim N, Hefti F, et al. Preclinical properties of 18F-AV-45: a PET agent for Abeta plaques in the brain. J Nucl Med. 2009;50(11):1887–94.PubMedCentralPubMedCrossRef
15.
Wong DF, Rosenberg PB, Zhou Y, Kumar A, Raymont V, Ravert HT, et al. In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18F-AV-45 (florbetapir [corrected] F18). J Nucl Med. 2010;51(6):913–20.PubMedCentralPubMedCrossRef
16.
Pontecorvo MJ, Mintun MA. PET amyloid imaging as a tool for early diagnosis and identifying patients at risk for progression to Alzheimer’s disease. Alzheimers Res Ther. 2011;3(2):11.PubMedCentralPubMedCrossRef
17.
Tateno A, Sakayori T, Kawashima Y, Higuchi M, Suhara T, Mizumura S, et al. Comparison of imaging biomarkers for Alzheimer’s disease: amyloid imaging with [18 F]florbetapir positron emission tomography and magnetic resonance imaging voxel-based analysis for entorhinal cortex atrophy. Int J Geriatr Psychiatry. 2015;30(5):505–13.PubMedCrossRef
18.
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology. 1984;34(7):939–44.PubMedCrossRef
19.
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–98.PubMedCrossRef
20.
Galasko D, Bennett D, Sano M, Ernesto C, Thomas R, Grundman M, et al. An inventory to assess activities of daily living for clinical trials in Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997;11(Suppl 2):S33–9.PubMedCrossRef
21.
Morris JC. The clinical dementia rating (CDR): current version and scoring rules. Neurology. 1993;43(11):2412–4.PubMedCrossRef
22.
Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer’s disease. Am J Psychiatry. 1984;141(11):1356–64.PubMedCrossRef
23.
Wechsler D. Wechsler memory scale-revised. San Antonio: The Psychological Corporation; 1987.
24.
Morris JC, Heyman A, Mohs RC, Hughes JP, van Belle G, Fillenbaum G, et al. The consortium to establish a registry for Alzheimer’s disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer’s disease. Neurology. 1989;39(9):1159–65.PubMedCrossRef
25.
Clark CM, Pontecorvo MJ, Beach TG, Bedell BJ, Coleman RE, Doraiswamy PM, et al. Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: a prospective cohort study. Lancet Neurol. 2012;11(8):669–78.PubMedCrossRef
26.
27.
Joshi AD, Pontecorvo MJ, Clark CM, Carpenter AP, Jennings DL, Sadowsky CH, et al. Performance characteristics of amyloid PET with florbetapir F18 in patients with Alzheimer’s disease and cognitively normal subjects. J Nucl Med. 2012;53(3):378–84.PubMedCrossRef
28.
Fleisher AS, Chen K, Liu X, Roontiva A, Thiyyagura P, Ayutyanont N, et al. Using positron emission tomography and florbetapir F18 to image cortical amyloid in patients with mild cognitive impairment or dementia due to Alzheimer disease. Arch Neurol. 2011;68(11):1404–11.PubMedCrossRef
29.
Joshi AD, Pontecorvo MJ, Lu M, Grundman M, Skovronsky DM, Mintun MA, et al. A semi-automated method for quantification of florbetapir F18 PET images. J Nucl Med. 2015 (accepted).
30.
Clark CM, Schneider JA, Bedell BJ, Beach TG, Bilker WB, Mintun MA, et al. Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA. 2011;305(3):275–83.PubMedCrossRef
31.
Bennett DA, Schneider JA, Bienias JL, Evans DA, Wilson RS. Mild cognitive impairment is related to Alzheimer disease pathology and cerebral infarctions. Neurology. 2005;64(5):834–41.PubMedCrossRef
32.
Gearing M, Schneider JA, Rebeck GW, Hyman BT, Mirra SS. Alzheimer’s disease with and without coexisting Parkinson’s disease changes: apolipoprotein E genotype and neuropathologic correlates. Neurology. 1995;45(11):1985–90.PubMedCrossRef
33.
Hulette CM, Welsh-Bohmer KA, Murray MG, Saunders AM, Mash DC, McIntyre LM. Neuropathological and neuropsychological changes in “normal” aging: evidence for preclinical Alzheimer disease in cognitively normal individuals. J Neuropathol Exp Neurol. 1998;57(12):1168–74.PubMedCrossRef
34.
Knopman DS, Parisi JE, Salviati A, Floriach-Robert M, Boeve BF, Ivnik RJ, et al. Neuropathology of cognitively normal elderly. J Neuropathol Exp Neurol. 2003;62(11):1087–95.PubMed
35.
Lim A, Tsuang D, Kukull W, Nochlin D, Leverenz J, McCormick W, et al. Clinico-neuropathological correlation of Alzheimer’s disease in a community-based case series. J Am Geriatr Soc. 1999;47(5):564–9.PubMedCrossRef
36.
Petersen RC, Parisi JE, Dickson DW, Johnson KA, Knopman DS, Boeve BF, et al. Neuropathologic features of amnestic mild cognitive impairment. Arch Neurol. 2006;63(5):665–72.PubMedCrossRef
37.
Price JL, Morris JC. Tangles and plaques in nondemented aging and “preclinical” Alzheimer’s disease. Ann Neurol. 1999;45(3):358–68.PubMedCrossRef
38.
Rasmusson DX, Brandt J, Steele C, Hedreen JC, Troncoso JC, Folstein MF. Accuracy of clinical diagnosis of Alzheimer disease and clinical features of patients with non-Alzheimer disease neuropathology. Alzheimer Dis Assoc Disord. 1996;10(4):180–8.PubMedCrossRef
39.
Schmitt FA, Davis DG, Wekstein DR, Smith CD, Ashford JW, Markesbery WR. “Preclinical” AD revisited: neuropathology of cognitively normal older adults. Neurology. 2000;55(3):370–6.PubMedCrossRef
40.
Johnson KA, Sperling RA, Gidicsin CM, Carmasin JS, Maye JE, Coleman RE, et al. Florbetapir (F18-AV-45) PET to assess amyloid burden in Alzheimer’s disease dementia, mild cognitive impairment, and normal aging. Alzheimers Dement. 2013;9(5 Suppl):S72–83.PubMedCentralPubMedCrossRef
41.
Doraiswamy PM, Sperling RA, Coleman RE, Johnson KA, Reiman EM, Davis MD, et al. Amyloid-beta assessed by florbetapir F18 PET and 18-month cognitive decline: a multicenter study. Neurology. 2012;79(16):1636–44.PubMedCrossRef
42.
Reiman EM, Chen K, Liu X, Bandy D, Yu M, Lee W, et al. Fibrillar amyloid-beta burden in cognitively normal people at 3 levels of genetic risk for Alzheimer’s disease. Proc Natl Acad Sci USA. 2009;106(16):6820–5.PubMedCentralPubMedCrossRef
43.
Lim A, Tsuang D, Kukull W, Nochlin D, Leverenz J, McCormick W, et al. Clinico-neuropathological correlation of Alzheimer’s disease in a community-based case series. J Am Geriatr Soc. 1999;47(5):564–9.PubMedCrossRef
44.
Mayeux R, Saunders AM, Shea S, Mirra S, Evans D, Roses AD, et al. Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer’s disease. Alzheimer’s disease centers consortium on Apolipoprotein E and Alzheimer’s disease. N Engl J Med. 1998;338(8):506–11.PubMedCrossRef
45.
Ranginwala NA, Hynan LS, Weiner MF, White CL III. Clinical criteria for the diagnosis of Alzheimer disease: still good after all these years. Am J Geriatr Psychiatry. 2008;16(5):384–8.PubMedCrossRef
Metadata
Title
Imaging characteristics and safety of florbetapir (18F) in Japanese healthy volunteers, patients with mild cognitive impairment and patients with Alzheimer’s disease
Authors
Chihiro Namiki
Yasushi Takita
Atsushi Iwata
Toshimitsu Momose
Michio Senda
Yoshiro Okubo
Abhinay D. Joshi
Ming Lu
Abigail Agbulos
Christopher Breault
Michael J. Pontecorvo
Publication date
01-08-2015
Publisher
Springer Japan
Published in
Annals of Nuclear Medicine / Issue 7/2015
Print ISSN: 0914-7187
Electronic ISSN: 1864-6433
DOI
https://doi.org/10.1007/s12149-015-0978-2

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