Targeting mannose receptor expression on macrophages in atherosclerotic plaques of apolipoprotein E-knockout mice using 111In-tilmanocept
| Autor: | David R. Vera, Miriam Braeuer, Zohreh Varasteh, Zhengtao Qin, Jonathan Vigne, Jean-Etienne Fabre, Markus Schwaiger, Dominique Le Guludec, Fabien Hyafil, Katja Steiger, Yvonne Döring, Rachida Aid-Launais, Yuanfang Li, Stephan G. Nekolla, Sarajo Mohanta, Nadège Anizan, Devy Diallo, Andreas J. R. Habenicht |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Apolipoprotein E
lcsh:Medical physics. Medical radiology. Nuclear medicine Pathology medicine.medical_specialty Apolipoprotein B lcsh:R895-920 Spleen 030204 cardiovascular system & hematology 030218 nuclear medicine & medical imaging 03 medical and health sciences 0302 clinical medicine Tilmanocept In vivo Non-invasive imaging medicine Radiology Nuclear Medicine and imaging Original Research Inflammation M2 differentiated macrophages biology business.industry SPECT/CT Atherosclerosis 3. Good health ddc medicine.anatomical_structure biology.protein Immunohistochemistry Lymph business Ex vivo Mannose receptor |
| Zdroj: | EJNMMI Research, Vol 7, Iss 1, Pp 1-9 (2017) EJNMMI Research |
| Popis: | Background Atherosclerotic plaque phenotypes are classified based on the extent of macrophage infiltration into the lesions, and the presence of certain macrophage subsets might be a sign for plaque vulnerability. The mannose receptor (MR) is over-expressed in activated macrophages. Tilmanocept is a tracer that targets MR and is approved in Europe and the USA for the detection of sentinel lymph nodes. In this study, our aim was to evaluate the potential of 111In-labelled tilmanocept for the detection of MR-positive macrophages in atherosclerotic plaques of apolipoprotein E-knockout (ApoE-KO) mouse model. Methods Tilmanocept was labelled with 111In. The labelling stability and biodistribution of the tracer was first evaluated in control mice (n = 10) 1 h post injection (p.i.). For in vivo imaging studies, 111In-tilmanocept was injected into ApoE-KO (n = 8) and control (n = 8) mice intravenously (i.v.). The mice were scanned 90 min p.i. using a dedicated animal SPECT/CT. For testing the specificity of 111In-tilmanocept uptake in plaques, a group of ApoE-KO mice was co-injected with excess amount of non-labelled tilmanocept. For ex vivo imaging studies, the whole aortas (n = 9 from ApoE-KO and n = 4 from control mice) were harvested free from adventitial tissue for Sudan IV staining and autoradiography. Cryosections were prepared for immunohistochemistry (IHC). Results 111In radiolabelling of tilmanocept provided a yield of greater than 99%. After i.v. injection, 111In-tilmanocept accumulated in vivo in MR-expressing organs (i.e. liver and spleen) and showed only low residual blood signal 1 h p.i. MR-binding specificity in receptor-positive organs was demonstrated by a 1.5- to 3-fold reduced uptake of 111In-tilmanocept after co-injection of a blocking dose of non-labelled tilmanocept. Focal signal was detected in atherosclerotic plaques of ApoE-KO mice, whereas no signal was detected in the aortas of control mice. 111In-tilmanocept uptake was detected in atherosclerotic plaques on autoradiography correlating well with Sudan IV-positive areas and associating with subendothelial accumulations of MR-positive macrophages as demonstrated by IHC. Conclusions After i.v. injection, 111In-tilmanocept accumulated in MR-expressing organs and was associated with only low residual blood signal. In addition, 111In-tilmanocept uptake was detected in atherosclerotic plaques of mice containing MR-expressing macrophages suggesting that tilmanocept represents a promising tracer for the non-invasive detection of macrophages in atherosclerotic plaques. |
| Databáze: | OpenAIRE |
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