Molecular Imaging of a New Multimodal Microbubble for Adhesion Molecule Targeting

Mona Ahmed, Björn Gustafsson, Silvia Aldi, Philip Dusart, G. Egri, Lynn M. Butler, Dianna Bone, Lars Dähne, Ulf Hedin, Kenneth Caidahl

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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 99mTc-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.

Original languageEnglish
JournalCellular and Molecular Bioengineering
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Adhesion Molecules
Molecular imaging
Microbubbles
Endothelial Cells
Molecular Imaging
Endothelial cells
Adhesion
Imaging
Inflammation
Molecules
Vascular Cell Adhesion Molecule-1
Antibody
Antibodies
SPECT
Macrophage
E-Selectin
Macrophages
Intercellular Adhesion Molecule-1
Single-Photon Emission-Computed Tomography
Peritonitis

Keywords

  • Antibodies
  • Confocal microscopy
  • Contrast agent
  • Endothelial cells
  • Flow cytometry
  • In vitro
  • In vivo
  • Inflammation
  • Macrophages
  • Polyvinyl-alcohol

ASJC Scopus subject areas

  • Modelling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Molecular Imaging of a New Multimodal Microbubble for Adhesion Molecule Targeting. / Ahmed, Mona; Gustafsson, Björn; Aldi, Silvia; Dusart, Philip; Egri, G.; Butler, Lynn M.; Bone, Dianna; Dähne, Lars; Hedin, Ulf; Caidahl, Kenneth.

In: Cellular and Molecular Bioengineering, 01.01.2018.

Research output: Contribution to journalArticle

Ahmed, Mona ; Gustafsson, Björn ; Aldi, Silvia ; Dusart, Philip ; Egri, G. ; Butler, Lynn M. ; Bone, Dianna ; Dähne, Lars ; Hedin, Ulf ; Caidahl, Kenneth. / Molecular Imaging of a New Multimodal Microbubble for Adhesion Molecule Targeting. In: Cellular and Molecular Bioengineering. 2018.
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AU - Ahmed, Mona

AU - Gustafsson, Björn

AU - Aldi, Silvia

AU - Dusart, Philip

AU - Egri, G.

AU - Butler, Lynn M.

AU - Bone, Dianna

AU - Dähne, Lars

AU - Hedin, Ulf

AU - Caidahl, Kenneth

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N2 - 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 99mTc-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.

AB - 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 99mTc-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.

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KW - In vivo

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KW - Macrophages

KW - Polyvinyl-alcohol

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