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dc.contributor.author
Meletta, Romana
dc.contributor.author
Müller Herde, Adrienne
dc.contributor.author
Dennler, Patrick
dc.contributor.author
Fischer, Eliane
dc.contributor.author
Schibli, Roger
dc.contributor.author
Krämer, Stefanie-Dorothea
dc.date.accessioned
2019-03-11T08:00:59Z
dc.date.available
2017-06-11T22:51:57Z
dc.date.available
2019-03-11T08:00:59Z
dc.date.issued
2016
dc.identifier.issn
2191-219X
dc.identifier.other
10.1186/s13550-015-0157-4
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/109828
dc.identifier.doi
10.3929/ethz-b-000109828
dc.description.abstract
Background The inflammatory nature of atherosclerosis provides a broad range of potential molecular targets for atherosclerosis imaging. Growing interest is focused on targets related to plaque vulnerability such as the co-stimulatory molecules CD80 and CD86. We investigated in this preclinical proof-of-concept study the applicability of the CD80/CD86-binding fusion protein belatacept as a probe for atherosclerosis imaging. Methods Belatacept was labeled with indium-111, and the binding affinity was determined with CD80/CD86-positive Raji cells. In vivo distribution was investigated in Raji xenograft-bearing mice in single-photon emission computed tomography (SPECT)/CT scans, biodistribution, and ex vivo autoradiography studies. Ex vivo SPECT/CT experiments were performed with aortas and carotids of ApoE KO mice. Accumulation in human carotid atherosclerotic plaques was investigated by in vitro autoradiography. Results 111In-DOTA-belatacept was obtained in >70 % yield, >99 % radiochemical purity, and ~40 GBq/μmol specific activity. The labeled belatacept bound with high affinity to Raji cells. In vivo, 111In-DOTA-belatacept accumulated specifically in Raji xenografts, lymph nodes, and salivary glands. Ex vivo SPECT experiments revealed displaceable accumulation in atherosclerotic plaques of ApoE KO mice fed an atherosclerosis-promoting diet. In human plaques, binding correlated with the infiltration by immune cells and the presence of a large lipid and necrotic core. Conclusions 111In-DOTA-belatacept accumulates in CD80/CD86-positive tissues in vivo and in vitro rendering it a research tool for the assessment of inflammatory activity in atherosclerosis and possibly other diseases. The tracer is suitable for preclinical imaging of co-stimulatory molecules of both human and murine origin. Radiolabeled belatacept could serve as a benchmark for future CD80/CD86-specific imaging agents.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Springer
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Co-stimulatory molecules
en_US
dc.subject
CD80
en_US
dc.subject
CD86
en_US
dc.subject
Belatacept
en_US
dc.subject
Atherosclerosis
en_US
dc.subject
Inflammation
en_US
dc.subject
Imaging
en_US
dc.title
Preclinical imaging of the co-stimulatory molecules CD80 and CD86 with indium-111-labeled belatacept in atherosclerosis
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2016-01-04
ethz.journal.title
EJNMMI Research
ethz.journal.volume
6
en_US
ethz.journal.abbreviated
EJNMMI res.
ethz.pages.start
1
en_US
ethz.size
12 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Berlin
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03688 - Schibli, Roger / Schibli, Roger
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::08830 - Krämer, Stefanie (Tit.-Prof.)
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03688 - Schibli, Roger / Schibli, Roger
ethz.date.deposited
2017-06-11T22:52:35Z
ethz.source
ECIT
ethz.identifier.importid
imp593653e9406d149172
ethz.ecitpid
pub:170961
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-13T19:24:17Z
ethz.rosetta.lastUpdated
2019-03-11T08:01:19Z
ethz.rosetta.versionExported
true
ethz.COinS
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