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EJNMMI Research

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Open Access 01-12-2014 | Original research

Imaging VEGF receptor expression to identify accelerated atherosclerosis

Authors: Yared Tekabe, Maria Kollaros, Adam Zerihoun, Geping Zhang, Marina V Backer, Joseph M Backer, Lynne L Johnson

Published in: EJNMMI Research | Issue 1/2014

Abstract

Background

The biology of the vulnerable plaque includes increased inflammation and rapid growth of vasa vasorum, processes that are associated with enhanced vascular endothelial growth factor (VEGF)/ imaging receptors for VEGF (VEGFR) signaling and are accelerated in diabetes. This study was designed to test the hypothesis that VEGFRs in atherosclerotic plaques with a SPECT tracer scVEGF-PEG-DOTA/^99mTc (scV/Tc) can identify accelerated atherosclerosis in diabetes.

Methods

Male apolipoprotein E null (ApoE^−/−) mice (6 weeks of age) were made diabetic (n = 10) or left as non-diabetic (n = 13). At 26 to 28 weeks of age, 5 non-diabetic mice were injected with functionally inactivated scV/Tc (in-scV/Tc) that does not bind to VEGF receptors, while 8 non-diabetic and 10 diabetic mice were injected with scV/Tc. After blood pool clearance, at 3 to 4 h post-injection, mice were injected with CT contrast agent and underwent SPECT/CT imaging. From the scans, regions of interest (ROI) were drawn on serial transverse sections comprising the proximal aorta and the percentage of injected dose (%ID) in ROIs was calculated. At the completion of imaging, mice were euthanized, proximal aorta explanted for gamma well counting to determine the percentage of injected dose per gram (%ID/g) uptake and immunohistochemical characterization.

Results

The uptake of scV/Tc in the proximal aorta, calculated from SPECT/CT co-registered scans as %ID, was significantly higher in the diabetic mice (0.036 ± 0.017%ID) compared to non-diabetic mice (0.017 ± 0.005%ID; P < 0.01), as was uptake measured as %ID/g in harvested aorta, 1.81 ± 0.50%ID/g in the diabetic group vs. 0.98 ± 0.25%ID/g in the non-diabetic group (P < 0.01). The nonspecific uptake of in-scV/Tc in proximal aorta was significantly lower than the uptake of functionally active scV/Tc. Immunostaining of the atherosclerotic lesions showed higher expression of VEGFR-1 and VEGFR-2 in the diabetic mice.

Conclusion

These initial results suggest that imaging VEGFR with scV/Tc shows promise as a non-invasive approach to identify accelerated atherosclerosis.

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Title: Imaging VEGF receptor expression to identify accelerated atherosclerosis
Authors: Yared Tekabe
Maria Kollaros
Adam Zerihoun
Geping Zhang
Marina V Backer
Joseph M Backer
Lynne L Johnson
Publication date: 01-12-2014
Publisher: Springer Berlin Heidelberg
Published in: EJNMMI Research / Issue 1/2014
Electronic ISSN: 2191-219X
DOI: https://doi.org/10.1186/s13550-014-0041-7

At a glance: The STEP trials

Springer Medicine

Imaging VEGF receptor expression to identify accelerated atherosclerosis

Abstract

Background

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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