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Manook, A.* ; Yousefi, B.H.* ; Willuweit, A.* ; Platzer, S.* ; Reder, S.* ; Voss, A. ; Huisman, M.* ; Settles, M.* ; Neff, F.* ; Velden, J.* ; Schoor, M.* ; von der Kammer, H.* ; Wester, H.J.* ; Schwaiger, M.* ; Henriksen, G.* ; Drzezga, A..*

Small-animal PET imaging of amyloid-beta plaques with [11C]PiB and its multi-modal validation in an APP/PS1 mouse model of Alzheimer's disease.

PLoS ONE 7:e31310 (2012)
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In vivo imaging and quantification of amyloid-β plaque (Aβ) burden in small-animal models of Alzheimer's disease (AD) is a valuable tool for translational research such as developing specific imaging markers and monitoring new therapy approaches. Methodological constraints such as image resolution of positron emission tomography (PET) and lack of suitable AD models have limited the feasibility of PET in mice. In this study, we evaluated a feasible protocol for PET imaging of Aβ in mouse brain with [(11)C]PiB and specific activities commonly used in human studies. In vivo mouse brain MRI for anatomical reference was acquired with a clinical 1.5 T system. A recently characterized APP/PS1 mouse was employed to measure Aβ at different disease stages in homozygous and hemizygous animals. We performed multi-modal cross-validations for the PET results with ex vivo and in vitro methodologies, including regional brain biodistribution, multi-label digital autoradiography, protein quantification with ELISA, fluorescence microscopy, semi-automated histological quantification and radioligand binding assays. Specific [(11)C]PiB uptake in individual brain regions with Aβ deposition was demonstrated and validated in all animals of the study cohort including homozygous AD animals as young as nine months. Corresponding to the extent of Aβ pathology, old homozygous AD animals (21 months) showed the highest uptake followed by old hemizygous (23 months) and young homozygous mice (9 months). In all AD age groups the cerebellum was shown to be suitable as an intracerebral reference region. PET results were cross-validated and consistent with all applied ex vivo and in vitro methodologies. The results confirm that the experimental setup for non-invasive [(11)C]PiB imaging of Aβ in the APP/PS1 mice provides a feasible, reproducible and robust protocol for small-animal Aβ imaging. It allows longitudinal imaging studies with follow-up periods of approximately one and a half years and provides a foundation for translational Alzheimer neuroimaging in transgenic mice.
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Publication type Article: Journal article
Document type Scientific Article
Keywords POSITRON-EMISSION-TOMOGRAPHY; PITTSBURGH COMPOUND-B; IN-VIVO DETECTION; TRANSGENIC MICE; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; PRECURSOR-PROTEIN; A-BETA; ASSOCIATION WORKGROUPS; PRESENILIN-1 TRANSGENES
Language english
Publication Year 2012
HGF-reported in Year 2012
ISSN (print) / ISBN 1932-6203
Journal PLoS ONE
Quellenangaben Volume: 7, Issue: 3, Pages: , Article Number: e31310 Supplement: ,
Publisher Public Library of Science (PLoS)
Publishing Place Lawrence, Kan.
Reviewing status Peer reviewed
Institute(s) Research Unit Analytical Pathology (AAP)
Institute of Pathology (PATH)
POF-Topic(s) 30205 - Bioengineering and Digital Health
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-500390-001
G-500300-001
PubMed ID 22427802
DOI 10.1371/journal.pone.0031310
WOS ID 000303062800004
Scopus ID 84857959777
Erfassungsdatum 2012-04-25
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