TY - JOUR
T1 - Evaluation of a dimeric-cRGD peptide for targeted PET-CT imaging of peripheral angiogenesis in diabetic mice
AU - Hedhli, Jamila
AU - Slania, Stephanie L.L.
AU - Płoska, Agata
AU - Czerwinski, Andrzej
AU - Konopka, Christian J.
AU - Wozniak, Marcin
AU - Banach, Maciej
AU - Dobrucki, Iwona T.
AU - Kalinowski, Leszek
AU - Dobrucki, Lawrence W.
N1 - Funding Information:
Our studies were funded by AHA Scientist Development Grant (10SDG4180043, LWD), Arnold Beckman Foundation (LWD, ID, JH), Ministry of Science and Higher Education Poland (“Mobility Plus” Program, AP; DIR/WK/2017/01, LK, LWD), Foundation for Polish Science (TEAM/2011-7/5, LK, MW), and Peptides International Inc. We thank John A. Cole for help with the manuscript edits.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - The αV β3 integrin plays an important role in many physiological functions and pathological disorders. αV 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 αV 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 αV 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 αV 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.
AB - The αV β3 integrin plays an important role in many physiological functions and pathological disorders. αV 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 αV 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 αV 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 αV 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.
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U2 - 10.1038/s41598-018-23372-9
DO - 10.1038/s41598-018-23372-9
M3 - Article
C2 - 29599497
AN - SCOPUS:85044567733
SN - 2045-2322
VL - 8
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 5401
ER -