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

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

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

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 ( 68 Ga)-labelled anti-MR nanobody ( 68 Ga-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 68 Ga 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, 68 Ga-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. 68 Ga-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: 68 Ga-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.

Original languageEnglish
Article number5
JournalEJNMMI Research
Volume9
DOIs
StatePublished - 2019

Keywords

  • Alternatively differentiated macrophages
  • Atherosclerotic plaques
  • Inflammation
  • Mannose receptor
  • Non-invasive imaging
  • PET/CT

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