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 language | English |
|---|---|
| Journal | Cellular and Molecular Bioengineering |
| DOIs | |
| Publication status | Accepted/In press - Jan 1 2018 |
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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 journal › Article
}
TY - JOUR
T1 - Molecular Imaging of a New Multimodal Microbubble for Adhesion Molecule Targeting
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
PY - 2018/1/1
Y1 - 2018/1/1
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.
KW - Antibodies
KW - Confocal microscopy
KW - Contrast agent
KW - Endothelial cells
KW - Flow cytometry
KW - In vitro
KW - In vivo
KW - Inflammation
KW - Macrophages
KW - Polyvinyl-alcohol
UR - http://www.scopus.com/inward/record.url?scp=85057585819&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85057585819&partnerID=8YFLogxK
U2 - 10.1007/s12195-018-00562-z
DO - 10.1007/s12195-018-00562-z
M3 - Article
AN - SCOPUS:85057585819
JO - Cellular and Molecular Bioengineering
JF - Cellular and Molecular Bioengineering
SN - 1865-5025
ER -