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Published in: Annals of Nuclear Medicine 2/2015

01-02-2015 | Original Article

Investigation of 11C-PiB equivocal PET findings

Authors: Chisa Hosokawa, Kazunari Ishii, Tomoko Hyodo, Kenta Sakaguchi, Kimio Usami, Kenji Shimamoto, Yuzuru Yamazoe, Makoto Hosono, Kazushi Hanada, Masami Ueda, Kazuma Saigo, Takamichi Murakami

Published in: Annals of Nuclear Medicine | Issue 2/2015

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Abstract

Objective

We have encountered occasional equivocal findings when assessing cerebral cortical amyloid retention with 11C-Pittsburgh compound B (PiB) PET. We investigated the diagnostic significance of equivocal PiB PET findings.

Methods

This retrospective study included 101 consecutive patients complaining of cognitive disorders (30 Alzheimer’s disease, 25 mild cognitive impairment, 8 Lewy body disease, 7 frontotemporal lobar degeneration, 31 others) who underwent both 11C-PiB PET and 18F-fluorodeoxy-d-glucose (FDG) PET. We visually classified PiB-positive, PiB-equivocal or PiB-negative ratings according to cortical uptake. For quantitative assessments of PiB PET, standard uptake values referred to cerebellar cortex (SUVR) were calculated in regional template volume of interests (frontal, temporoparietal, precuneus/posterior cingulate cortex, cerebral white matter and cerebellar cortex). The results of visual assessment were compared with the regional and mean cortical SUVRs and cortical-to-white matter ratio of PiB uptake, as well as clinical and FDG PET findings.

Results

Among the 101 scans, 41 were PiB negative, 11 were PiB equivocal, and 49 were rated PiB positive in the visual assessments. The mean cortical SUVR and cortical-to-white matter ratio were 0.97 ± 0.07 and 0.57 ± 0.21 in PiB-negative, 1.51 ± 0.17 and 0.75 ± 0.06 in PiB equivocal and 2.10 ± 0.33 and 0.97 ± 0.11 in PiB-positive group, respectively. Nine of 11 subjects with PiB-equivocal findings had cognitive impairments and FDG distribution compatible with Alzheimer’s disease or dementia with Lewy bodies.

Conclusions

We considered equivocal visual findings on PiB PET equivalent to PiB-positive with slight cortical uptake. In addition, slight cortical amyloid deposits were considered to cause cerebral metabolic abnormality and cognitive impairment. Although mean cortical SUVR was more sensitive than visual assessment because of low cortical-to-white matter contrast due to non-specific accumulation in white matter, it is important not to overlook small amounts of cortical uptake of PiB in visual inspection for exact diagnosis.
Literature
1.
go back to reference Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburg compound-B. Ann Neurol. 2004;55:306–19.CrossRefPubMed Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburg compound-B. Ann Neurol. 2004;55:306–19.CrossRefPubMed
2.
3.
go back to reference Price JC, Klunk WE, Lopresti BJ, Lu X, Hoge JA, Ziolko S, et al. Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh Compound B. J Cereb Blood Flow Metabol. 2005;25:1528–47.CrossRef Price JC, Klunk WE, Lopresti BJ, Lu X, Hoge JA, Ziolko S, et al. Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh Compound B. J Cereb Blood Flow Metabol. 2005;25:1528–47.CrossRef
4.
go back to reference Yaqub M, Tolboom N, Boellaard R, van Berckel BNM, van Triburg EW, Luurtsema G, et al. Simplified parametric methods for [11C] PIB studies. Neuroimage. 2008;42:76–86.CrossRefPubMed Yaqub M, Tolboom N, Boellaard R, van Berckel BNM, van Triburg EW, Luurtsema G, et al. Simplified parametric methods for [11C] PIB studies. Neuroimage. 2008;42:76–86.CrossRefPubMed
5.
go back to reference Lopresti BJ, Klunk WE, Mathis CA, Hoge JA, Ziolko SK, Lu X, et al. Simplified quantitation of Pittsburgh compound B amyloid imaging PET studies: a comparable analysis. J Nucl Med. 2005;46:1959–72.PubMed Lopresti BJ, Klunk WE, Mathis CA, Hoge JA, Ziolko SK, Lu X, et al. Simplified quantitation of Pittsburgh compound B amyloid imaging PET studies: a comparable analysis. J Nucl Med. 2005;46:1959–72.PubMed
6.
go back to reference Van Berckel BNM, Ossenkoppele R, Tolboom N, Yaqub M, Foster-Dingley JC, Windhorst AD, et al. Longitudinal amyloid imaging using 11C-PiB: methodological consideration. J Nucl Med. 2013;54:1570–6.CrossRefPubMed Van Berckel BNM, Ossenkoppele R, Tolboom N, Yaqub M, Foster-Dingley JC, Windhorst AD, et al. Longitudinal amyloid imaging using 11C-PiB: methodological consideration. J Nucl Med. 2013;54:1570–6.CrossRefPubMed
7.
go back to reference McKhann G, Drachman D, Foistein M, Katzman R, Price D, Stadian 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;34:939.CrossRefPubMed McKhann G, Drachman D, Foistein M, Katzman R, Price D, Stadian 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;34:939.CrossRefPubMed
8.
go back to reference McKeith IG, Dickson DW, Lowe J, Emre M, O’Brien JT, Feldman H, et al. Diagnosis and management of dementia with Lewy bodies. Third report of the DLB consortium. Neurology. 2005;65:1863–72.CrossRefPubMed McKeith IG, Dickson DW, Lowe J, Emre M, O’Brien JT, Feldman H, et al. Diagnosis and management of dementia with Lewy bodies. Third report of the DLB consortium. Neurology. 2005;65:1863–72.CrossRefPubMed
9.
go back to reference Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, et al. Current concepts in mild cognitive impairment. Arch Neurol. 2001;58:1985–92.CrossRefPubMed Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, et al. Current concepts in mild cognitive impairment. Arch Neurol. 2001;58:1985–92.CrossRefPubMed
10.
go back to reference Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, et al. Frontotemporal lobar degeneration—a consensus on clinical diagnostic criteria. Neurology. 1998;51:1546–54.CrossRefPubMed Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, et al. Frontotemporal lobar degeneration—a consensus on clinical diagnostic criteria. Neurology. 1998;51:1546–54.CrossRefPubMed
11.
go back to reference Mathis CA, Wang Y, Holt DP, Huang GF, Debnath ML, Klunk WE. Synthesis and evaluation of 11C-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents. J Med Chem. 2003;46:2740–54.CrossRefPubMed Mathis CA, Wang Y, Holt DP, Huang GF, Debnath ML, Klunk WE. Synthesis and evaluation of 11C-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents. J Med Chem. 2003;46:2740–54.CrossRefPubMed
12.
go back to reference Federo-Tavoletti MT, Rowe CC, McLean CA, Leone L, Li QX, Masters CL, et al. Characterization of PiB binding to white matter in Alzheimer disease and other dementias. J Nucl Med. 2009;50:198–204.CrossRef Federo-Tavoletti MT, Rowe CC, McLean CA, Leone L, Li QX, Masters CL, et al. Characterization of PiB binding to white matter in Alzheimer disease and other dementias. J Nucl Med. 2009;50:198–204.CrossRef
13.
go back to reference Minoshima S, Giordani B, Berent S, Frey KA, Foster NL, Kuhl DE. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer’s disease. Ann Neurol. 1997;42:85–94.CrossRefPubMed Minoshima S, Giordani B, Berent S, Frey KA, Foster NL, Kuhl DE. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer’s disease. Ann Neurol. 1997;42:85–94.CrossRefPubMed
14.
go back to reference Minoshima S, Foster NL, Petrie EC, Albin RL, Frey KA, Kuhl DE. Neuroimaging in dementia with Lewy bodies; metabolism, neurochemistry, and morphology. J Geriatr Psychiatry Neurol. 2002;15:200–9.CrossRefPubMed Minoshima S, Foster NL, Petrie EC, Albin RL, Frey KA, Kuhl DE. Neuroimaging in dementia with Lewy bodies; metabolism, neurochemistry, and morphology. J Geriatr Psychiatry Neurol. 2002;15:200–9.CrossRefPubMed
15.
go back to reference Ikonomovic MD, Klunk WE, Abrahamson EE, Mathis CA, Price JC, Tsopelas ND, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease. Brain. 2008;131:1630–45.CrossRefPubMedCentralPubMed Ikonomovic MD, Klunk WE, Abrahamson EE, Mathis CA, Price JC, Tsopelas ND, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease. Brain. 2008;131:1630–45.CrossRefPubMedCentralPubMed
16.
go back to reference Ng S, Villemagne VL, Berlangieri S, Lee ST, Cherk M, Gong SJ, et al. Visual assessment versus quantitative assessment of 11C-PIB PET and 18F-FDG PET for detection of Alzheimer’s disease. J Nucl Med. 2007;48:547–52.CrossRefPubMed Ng S, Villemagne VL, Berlangieri S, Lee ST, Cherk M, Gong SJ, et al. Visual assessment versus quantitative assessment of 11C-PIB PET and 18F-FDG PET for detection of Alzheimer’s disease. J Nucl Med. 2007;48:547–52.CrossRefPubMed
17.
go back to reference Suotunen T, Hirvonen J, Immonen-Raiha P, Aalto S, Lisinen I, Arponen E, et al. Visual assessment of [11C]-PIB PET in patients with cognitive impairment. Eur J Nucl Med Mol Imaging. 2010;37:1141–7.CrossRefPubMed Suotunen T, Hirvonen J, Immonen-Raiha P, Aalto S, Lisinen I, Arponen E, et al. Visual assessment of [11C]-PIB PET in patients with cognitive impairment. Eur J Nucl Med Mol Imaging. 2010;37:1141–7.CrossRefPubMed
18.
go back to reference Mormino EC, Brandel MG, Madison CM, Rabinovici GD, Marks S, Baker SL, et al. Not quite PIB-positive, not quite PIB-negative: slight PIB elevations in elderly normal control subjects are biologically relevant. Neuroimage. 2012;59:1152–60.CrossRefPubMedCentralPubMed Mormino EC, Brandel MG, Madison CM, Rabinovici GD, Marks S, Baker SL, et al. Not quite PIB-positive, not quite PIB-negative: slight PIB elevations in elderly normal control subjects are biologically relevant. Neuroimage. 2012;59:1152–60.CrossRefPubMedCentralPubMed
19.
go back to reference Cohen AD, Mowrey W, Weissfeld LA, Aizenstein HJ, McDade E, Mountz JM, et al. Classification of amyloid-positivity in controls: comparison of visual read and quantitative approaches. Neuroimage. 2013;71:207–15.CrossRefPubMedCentralPubMed Cohen AD, Mowrey W, Weissfeld LA, Aizenstein HJ, McDade E, Mountz JM, et al. Classification of amyloid-positivity in controls: comparison of visual read and quantitative approaches. Neuroimage. 2013;71:207–15.CrossRefPubMedCentralPubMed
20.
go back to reference Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82:239–59.CrossRefPubMed Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82:239–59.CrossRefPubMed
21.
go back to reference Villemagne VL, Klunk WE, Mathis CA, Rowe CC, Brooks DJ, Hyman BT, et al. Aβ Imaging: feasible, pertinent, and vital to progress in Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2012;39:209–19.CrossRefPubMedCentralPubMed Villemagne VL, Klunk WE, Mathis CA, Rowe CC, Brooks DJ, Hyman BT, et al. Aβ Imaging: feasible, pertinent, and vital to progress in Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2012;39:209–19.CrossRefPubMedCentralPubMed
Metadata
Title
Investigation of 11C-PiB equivocal PET findings
Authors
Chisa Hosokawa
Kazunari Ishii
Tomoko Hyodo
Kenta Sakaguchi
Kimio Usami
Kenji Shimamoto
Yuzuru Yamazoe
Makoto Hosono
Kazushi Hanada
Masami Ueda
Kazuma Saigo
Takamichi Murakami
Publication date
01-02-2015
Publisher
Springer Japan
Published in
Annals of Nuclear Medicine / Issue 2/2015
Print ISSN: 0914-7187
Electronic ISSN: 1864-6433
DOI
https://doi.org/10.1007/s12149-014-0924-8

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