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Evaluation of a dimeric-cRGD peptide for targeted PET-CT imaging of peripheral angiogenesis in diabetic mice.

Evaluation of a dimeric-cRGD peptide for targeted PET-CT imaging of peripheral angiogenesis in diabetic mice.
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Hedhli J, Slania SLL, Płoska A, Czerwinski A, Konopka CJ, Wozniak M, Banach M, Dobrucki IT, Kalinowski L, Dobrucki LW,


Hedhli J, Slania SLL, Płoska A, Czerwinski A, Konopka CJ, Wozniak M, Banach M, Dobrucki IT, Kalinowski L, Dobrucki LW, (click to view)

Hedhli J, Slania SLL, Płoska A, Czerwinski A, Konopka CJ, Wozniak M, Banach M, Dobrucki IT, Kalinowski L, Dobrucki LW,

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Scientific reports 2018 03 298(1) 5401 doi 10.1038/s41598-018-23372-9
Abstract

The α βintegrin plays an important role in many physiological functions and pathological disorders. α βis minimally expressed in normal quiescent endothelial cells, but significantly upregulated during neovascularization. In this study, we evaluated aCu-labeled dimeric cRGD tracer targeted at α βintegrin and report its applicability to assess peripheral angiogenesis in diabetes mellitus (DM). We established a murine model of type-1 DM characterized by elevated glucose, glycated serum protein (GSP), and glycated hemoglobin A1c (HbA1c). We demonstrated that our imaging probe is specific to α βintegrin under both normo- and hyperglycemic conditions. We found that the analysis of in vivo PET-CT images correlated well with gamma well counting (GWC). Both GWC and PET-CT imaging demonstrated increased uptake ofCu-NOTA-PEG4-cRGDin the ischemic hindlimb in contrast to non-ischemic control. GWC of the distal ischemic tissue from DM mice showed significantly lower probe accumulation than in non-DM mice. The immunofluorescence staining of the ischemic tissues showed a 3-fold reduction in CD31 and 4-fold reduction in the α βexpression in DM vs. non-DM animals. In conclusion, we successfully demonstrated that diabetes-associated reductions in peripheral angiogenesis can be non-invasively detected with PET-CT imaging using targeted dimeric-cRGD probe.

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