Academic Commons

Articles

Imaging receptor for advanced glycation end product expression in mouse model of hind limb ischemia

Zhang, Geping; Schmidt, Anne Marie; Johnson, Lynne L.; Tekabe, Yared; Kollaros, Maria; Li, Chong

Background: The purpose of this study is to image the effect of diabetes on expression of receptor for advanced glycation endproducts (RAGE) in limb ischemia in live animals. Methods: Male wild-type C57BL/6 mice were either made diabetic or left as control. Two months later, diabetic and non-diabetic mice underwent left femoral artery ligation. The right leg served as lesion control. Five days later, mice were injected with 15.1 ± 4.4 MBq 99mTc-anti-RAGE F(ab’)2 and 4 to 5 h later (blood pool clearance) underwent SPECT/CT imaging. At the completion of imaging, mice were euthanized, hind limbs counted and sectioned, and scans reconstructed. Regions of interest were drawn on serial transverse sections comprising the hind limbs and activity in millicuries summed and divided by the injected dose (ID). Quantitative histology was performed for RAGE staining and angiogenesis. Results: Uptake of 99mTc-anti-RAGE F(ab')2 as %ID × 10−3 was higher in the left (ischemic) limbs for the diabetic mice (n = 8) compared to non-diabetic mice (n = 8) (1.20 ± 0.44% vs. 0.49 ± 0.40%; P = 0.0007) and corresponded to less angiogenesis in the diabetic mice. Uptake was also higher in the right limbs of diabetic compared to non-diabetic animals (0.82 ± 0.33% vs. 0.40 ± 0.14%; P = 0.0004). Conclusions: These data show the feasibility of imaging and quantifying the effect of diabetes on RAGE expression in limb ischemia.

Files

  • thumnail for 012509c8d0cf70962070317441f309d0.zip 012509c8d0cf70962070317441f309d0.zip binary/octet-stream 2.77 MB Download File

Also Published In

Title
EJNMMI Research
DOI
https://doi.org/10.1186/2191-219X-3-37

More About This Work

Academic Units
Medicine
Publisher
Springer
Published Here
September 8, 2014

Notes

Limb ischemia, Diabetes, RAGE, Molecular imaging, Radionuclides