Evaluation of a dimeric-cRGD peptide for targeted PET-CT imaging of peripheral angiogenesis in diabetic mice
| Autor: | Agata Płoska, Leszek Kalinowski, Marcin Wozniak, Lawrence W. Dobrucki, Andrzej Czerwinski, Iwona T. Dobrucki, Jamila Hedhli, Stephanie Slania, Maciej Banach, Christian J. Konopka |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine CD31 Angiogenesis Integrin Neovascularization Physiologic lcsh:Medicine Hindlimb Peptides Cyclic Article Diabetes Mellitus Experimental Neovascularization Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation In vivo Positron Emission Tomography Computed Tomography Diabetes mellitus Human Umbilical Vein Endothelial Cells medicine Animals Humans Tissue Distribution lcsh:Science Multidisciplinary biology Chemistry lcsh:R Integrin alphaVbeta3 medicine.disease Mice Inbred C57BL Disease Models Animal 030104 developmental biology Microscopy Fluorescence 030220 oncology & carcinogenesis Cancer research biology.protein lcsh:Q Radiopharmaceuticals medicine.symptom Dimerization Biomarkers Protein Binding |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-13 (2018) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | The α V β3 integrin plays an important role in many physiological functions and pathological disorders. α V β3 is minimally expressed in normal quiescent endothelial cells, but significantly upregulated during neovascularization. In this study, we evaluated a 64Cu-labeled dimeric cRGD tracer targeted at α V β3 integrin 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 V β3 integrin 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 of 64Cu-NOTA-PEG4-cRGD2 in 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 V β3 expression 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. |
| Databáze: | OpenAIRE |
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