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Molecular Imaging of a New Multimodal Microbubble for Adhesion Molecule Targeting
Karolinska Inst, Dept Mol Med & Surg, Ctr Mol Med, S-17176 Stockholm, Sweden..
Karolinska Inst, Dept Mol Med & Surg, Ctr Mol Med, S-17176 Stockholm, Sweden..
Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden..
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Cellular and Clinical Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0003-2747-3214
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2019 (English)In: Cellular and Molecular Bioengineering, ISSN 1865-5025, E-ISSN 1865-5033, Vol. 12, no 1, p. 15-32Article in journal (Refereed) Published
Abstract [en]

Introduction: Inflammation is an important risk-associated component of many diseases and can be diagnosed by molecular imaging of specific molecules. The aim of this study was to evaluate the possibility of targeting adhesion molecules on inflammation-activated endothelial cells and macrophages using an innovative multimodal polyvinyl alcohol-based microbubble (MB) contrast agent developed for diagnostic use in ultrasound, magnetic resonance, and nuclear imaging. Methods: We assessed the binding efficiency of antibody-conjugated multimodal contrast to inflamed murine or human endothelial cells (ECs), and to peritoneal macrophages isolated from rats with peritonitis, utilizing the fluorescence characteristics of the MBs. Single-photon emission tomography (SPECT) was used to illustrate 99m Tc-labeled MB targeting and distribution in an experimental in vivo model of inflammation. Results: Flow cytometry and confocal microscopy showed that binding of antibody-targeted MBs to the adhesion molecules ICAM-1, VCAM-1, or E-selectin, expressed on cytokine-stimulated ECs, was up to sixfold higher for human and 12-fold higher for mouse ECs, compared with that of non-targeted MBs. Under flow conditions, both VCAM-1- and E-selectin-targeted MBs adhered more firmly to stimulated human ECs than to untreated cells, while VCAM-1-targeted MBs adhered best to stimulated murine ECs. SPECT imaging showed an approximate doubling of signal intensity from the abdomen of rats with peritonitis, compared with healthy controls, after injection of anti-ICAM-1-MBs. Conclusions: This novel multilayer contrast agent can specifically target adhesion molecules expressed as a result of inflammatory stimuli in vitro, and has potential for use in disease-specific multimodal diagnostics in vivo using antibodies against targets of interest.

Place, publisher, year, edition, pages
SPRINGER , 2019. Vol. 12, no 1, p. 15-32
Keywords [en]
Antibodies, Contrast agent, Confocal microscopy, Endothelial cells, Flow cytometry, Inflammation, In vitro, In vivo, Macrophages, Polyvinyl-alcohol
National Category
Medical Biotechnology
Identifiers
URN: urn:nbn:se:kth:diva-243933DOI: 10.1007/s12195-018-00562-zISI: 000456651000002Scopus ID: 2-s2.0-85057585819OAI: oai:DiVA.org:kth-243933DiVA, id: diva2:1296032
Note

QC 20190313

Available from: 2019-03-13 Created: 2019-03-13 Last updated: 2019-03-13Bibliographically approved

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Dusart, PhilipButler, Lynn M.

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