Targeting mannose receptor expression on macrophages in atherosclerotic plaques of apolipoprotein E-knockout mice using 68Ga-NOTA-anti-MMR nanobody: non-invasive imaging of atherosclerotic ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-12

AUTHORS

Zohreh Varasteh, Sarajo Mohanta, Yuanfang Li, Nicolás López Armbruster, Miriam Braeuer, Stephan G. Nekolla, Andreas Habenicht, Hendrik B. Sager, Geert Raes, Wolfgang Weber, Sophie Hernot, Markus Schwaiger

ABSTRACT

BACKGROUND: Rupture-prone atherosclerotic plaques are characterized by heavy macrophage infiltration, and the presence of certain macrophage subsets might be a sign for plaque vulnerability. The mannose receptor (MR, CD206) is over-expressed in several types of alternatively activated macrophages. In this study, our objective was to evaluate the feasibility of a Gallium-68 (68Ga)-labelled anti-MR nanobody (68Ga-anti-MMR Nb) for the visualization of MR-positive (MR+) macrophages in atherosclerotic plaques of apolipoprotein E-knockout (ApoE-KO) mice. RESULTS: NOTA-anti-MMR Nb was labelled with 68Ga with radiochemical purity > 95%. In vitro cell-binding studies demonstrated selective and specific binding of the tracer to M2a macrophages. For in vivo atherosclerotic plaque imaging studies, 68Ga-NOTA-anti-MMR Nb was injected into ApoE-KO and control mice intravenously (i.v.) and scanned 1 h post-injection for 30 min using a dedicated animal PET/CT. Focal signals could be detected in aortic tissue of ApoE-KO mice, whereas no signal was detected in the aortas of control mice. 68Ga-NOTA-anti-MMR Nb uptake was detected in atherosclerotic plaques on autoradiographs and correlated well with Sudan-IV-positive areas. The calculated ratio of plaque-to-normal aortic tissue autoradiographic signal intensity was 7.7 ± 2.6 in aortas excised from ApoE-KO mice. Immunofluorescence analysis of aorta cross-sections confirmed predominant MR expression in macrophages located in the fibrous cap layer and shoulder region of the plaques. CONCLUSIONS: 68Ga-NOTA-anti-MMR Nb allows non-invasive PET/CT imaging of MR expression in atherosclerotic lesions in a murine model and may represent a promising tool for clinical imaging and evaluation of plaque (in)stability. More... »

PAGES

5

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s13550-019-0474-0

DOI

http://dx.doi.org/10.1186/s13550-019-0474-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111577245

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30666513


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