Title |
Preclinical imaging of the co-stimulatory molecules CD80 and CD86 with indium-111-labeled belatacept in atherosclerosis
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Published in |
EJNMMI Research, January 2016
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DOI | 10.1186/s13550-015-0157-4 |
Pubmed ID | |
Authors |
Romana Meletta, Adrienne Müller Herde, Patrick Dennler, Eliane Fischer, Roger Schibli, Stefanie D. Krämer |
Abstract |
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. 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. (111)In-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, (111)In-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. (111)In-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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 30 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 5 | 17% |
Researcher | 5 | 17% |
Student > Bachelor | 5 | 17% |
Student > Doctoral Student | 2 | 7% |
Unspecified | 1 | 3% |
Other | 2 | 7% |
Unknown | 10 | 33% |
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Physics and Astronomy | 1 | 3% |
Other | 3 | 10% |
Unknown | 9 | 30% |