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EJNMMI Research
Published in: EJNMMI Research 1/2020

Open Access 01-12-2020 | Original research

VEGF receptor targeted imaging of angiogenic response to limb ischemia in diabetic vs. non-diabetic Yucatan minipigs

Authors: Lynne L. Johnson, Jordan Johnson, Ziad Ali, Yared Tekabe, Rebecca Ober, Gail Geist, Alicia McLuckie, Aram Safarov, April Holland, Geping Zhang, Marina Backer, Joseph Backer

Published in: EJNMMI Research | Issue 1/2020

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Abstract

Background

New therapies to treat diabetic peripheral artery disease (PAD) require target-specific non-invasive imaging modalities to follow efficacy. As a translational study, we performed targeted imaging of receptors for vascular endothelial growth factor (VEGF) in response to anterior femoral artery occlusion (FAO) in Yucatan minipigs and compare the normal response to response in diabetic Yucatan minipigs.

Methods

Eleven Yucatan minipigs, 6 non-diabetic (non-D) and 5 purpose bred diabetic (D) (Sinclair, Auxvasse MO), underwent intravascular total occlusion of the anterior femoral artery (FA). At days 1 and 28, pigs underwent SPECT/CT 201Tl hindlimb perfusion imaging and at day 7 were injected with [99mTc]DOTA-PEG-scVEGF (scV/Tc) tracer targeting VEGF receptor, and underwent biopsies of the hindlimb muscles for gamma counting and histology, followed by imaging. One day after the final scan, pigs underwent contrast angiography of the lower extremities. Counts from scans were converted to percentage injected activity (%IA).

Results

Perfusion was lower in the occluded hindlimb compared to non-occluded on day 1 in both the D and non-D pigs. At day 7, scV/Tc count ratio of counts from ROIs drawn in proximal gastrocnemius muscle for the occluded over non-occluded limb was significantly higher in non-D vs. D pigs (1.32 ± 0.06 vs. 1.04 ± 0.13, P = 0.02) reflecting higher level of angiogenesis. Perfusion increased between days 1 and 28 in the muscles in the occluded limb for the non-diabetic pigs while the diabetic pig showed no increase (+ 0.13 ± 0.08 %IA vs. − 0.13 ± 0.11, P = 0.003). The anterior FA showed poor contrast filling beyond occluder and qualitatively fewer bridging collaterals compared to non-D pigs at 28 days.

Conclusion

VEGF receptor targeted imaging showed the effects of diabetes to suppress angiogenesis in response to occlusion of the anterior femoral artery of purpose bred diabetic Yucatan minipigs and indicates potential applicability as a marker to follow efficacy of novel therapies to improve blood flow by stimulating angiogenesis in diabetic PAD.
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Metadata
Title
VEGF receptor targeted imaging of angiogenic response to limb ischemia in diabetic vs. non-diabetic Yucatan minipigs
Authors
Lynne L. Johnson
Jordan Johnson
Ziad Ali
Yared Tekabe
Rebecca Ober
Gail Geist
Alicia McLuckie
Aram Safarov
April Holland
Geping Zhang
Marina Backer
Joseph Backer
Publication date
01-12-2020
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2020
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-020-00626-0

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