Molecular Imaging of a New Multimodal Microbubble for Adhesion Molecule Targeting

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Molecular Imaging of a New Multimodal Microbubble for Adhesion Molecule Targeting

Ahmed, M. (author): Karolinska Institutet

Gustafsson, B. (author): Karolinska Institutet

Aldi, S. (author): Karolinska Institutet

Dusart, Philip (author): KTH,Cellulär och klinisk proteomik,Science for Life Laboratory, SciLifeLab

Egri, G. (author): Surflay Nanotec GmbH, Max Planck Str 3, D-12489 Berlin, Germany.

Butler, Lynn M. (author): Karolinska Institutet,KTH,Science for Life Laboratory, SciLifeLab,Cellulär och klinisk proteomik

Bone, D. (author): Karolinska Inst, Dept Mol Med & Surg, Ctr Mol Med, S-17176 Stockholm, Sweden.

Dahne, L. (author): Surflay Nanotec GmbH, Max Planck Str 3, D-12489 Berlin, Germany.

Hedin, U. (author): Karolinska Institutet

Caidahl, Kenneth, 1949 (author): Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,Karolinska Inst, Dept Mol Med & Surg, Ctr Mol Med, S-17176 Stockholm, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, S-41345 Gothenburg, Sweden.

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2018-11-28
2019
English.
In: Cellular and Molecular Bioengineering. - : Springer Science and Business Media LLC. - 1865-5025 .- 1865-5033. ; 12:1, s. 15-32

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Journal article (peer-reviewed)

Abstract Subject headings

IntroductionInflammation 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.MethodsWe 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 Tc-99m-labeled MB targeting and distribution in an experimental in vivo model of inflammation.ResultsFlow 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.ConclusionsThis 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology (hsv//eng)

Keyword

Antibodies
Contrast agent
Confocal microscopy
Endothelial cells
Flow cytometry
Inflammation
In
contrast agent
p-selectin
ultrasound
expression
mri
atherosclerosis
nanoparticles
peritonitis
zymosan
binding
Antibodies

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ref (subject category)
art (subject category)

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By the author/editor: Ahmed, M.; Gustafsson, B.; Aldi, S.; Dusart, Philip; Egri, G.; Butler, Lynn M.; show more...; Bone, D.; Dahne, L.; Hedin, U.; Caidahl, Kenneth ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Medical Biotechn ...

Articles in the publication: Cellular and Mol ...

By the university: University of Gothenburg; Royal Institute of Technology; Karolinska Institutet

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