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11C-PiB and 124I-an...
11C-PiB and 124I-antibody PET provide differing estimates of brain amyloid-β after therapeutic intervention
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- Meier, Silvio R. (author)
- Uppsala universitet,Geriatrik
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- Sehlin, Dag, 1976- (author)
- Uppsala universitet,Geriatrik
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- Roshanbin, Sahar, 1984- (author)
- Uppsala universitet,Geriatrik
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- Lim Falk, Victoria (author)
- Uppsala universitet,Geriatrik
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- Saito, Takashi (author)
- Laboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Wako, Japan; Department of Neurocognitive Science, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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- Saido, Takaomi C (author)
- Laboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Wako, Japan
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- Neumann, Ulf (author)
- Neuroscience Research, Novartis Institutes for BioMedical Research, Basel, Switzerland
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- Rokka, Johanna (author)
- Uppsala universitet,Geriatrik
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- Eriksson, Jonas (author)
- Uppsala universitet,Preparativ läkemedelskemi,PET Centre, Uppsala University Hospital, Uppsala, Sweden
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- Syvänen, Stina (author)
- Uppsala universitet,Geriatrik
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(creator_code:org_t)
- 2021-06-04
- 2022
- English.
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In: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 63:2, s. 302-309
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Abstract
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- PET imaging of amyloid-β (Aβ) has become an important component of Alzheimer disease diagnosis. 11C-Pittsburgh compound B (11C-PiB) and analogs bind to fibrillar Aβ. However, levels of nonfibrillar, soluble, aggregates of Aβ appear more dynamic during disease progression and more affected by Aβ-reducing treatments. The aim of this study was to compare an antibody-based PET ligand targeting nonfibrillar Aβ with 11C-PiB after β-secretase (BACE-1) inhibition in 2 Alzheimer disease mouse models at an advanced stage of Aβ pathology.Methods: Transgenic ArcSwe mice (16 mo old) were treated with the BACE-1 inhibitor NB-360 for 2 mo, whereas another group was kept as controls. A third group was analyzed at the age of 16 mo as a baseline. Mice were PET-scanned with 11C-PiB to measure Aβ plaque load followed by a scan with the bispecific radioligand 124I-RmAb158-scFv8D3 to investigate nonfibrillar aggregates of Aβ. The same study design was then applied to another mouse model, AppNL-G-F. In this case, NB-360 treatment was initiated at the age of 8 mo and animals were scanned with 11C-PiB-PET and 125I-RmAb158-scFv8D3 SPECT. Brain tissue was isolated after scanning, and Aβ levels were assessed.Results: 124I-RmAb158-scFv8D3 concentrations measured with PET in hippocampus and thalamus of NB-360–treated ArcSwe mice were similar to those observed in baseline animals and significantly lower than concentrations observed in same-age untreated controls. Reduced 125I-RmAb158-scFv8D3 retention was also observed with SPECT in hippocampus, cortex, and cerebellum of NB-360–treated AppNL-G-F mice. Radioligand in vivo concentrations corresponded to postmortem brain tissue analysis of soluble Aβ aggregates. For both models, mice treated with NB-360 did not display a reduced 11C-PiB signal compared with untreated controls, and further, both NB-360 and control mice tended, although not reaching significance, to show higher 11C-PiB signal than the baseline groups.Conclusion: This study demonstrated the ability of an antibody-based radioligand to detect changes in brain Aβ levels after anti-Aβ therapy in ArcSwe and AppNL-G-F mice with pronounced Aβ pathology. In contrast, the decreased Aβ levels could not be quantified with 11C-PiB PET, suggesting that these ligands detect different pools of Aβ.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Alzheimer´s Disease
- BACE-1 inhibition
- Amyloid-beta
- 11C-PiB
- Antibody-based PET
Publication and Content Type
- ref (subject category)
- art (subject category)
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Meier, Silvio R.
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Sehlin, Dag, 197 ...
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Roshanbin, Sahar ...
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Lim Falk, Victor ...
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Saito, Takashi
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Saido, Takaomi C
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Neumann, Ulf
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Rokka, Johanna
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Eriksson, Jonas
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Syvänen, Stina
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
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Journal of Nucle ...
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Uppsala University