Abstract 20683: Imaging Rage Expression In Mouse Model Of Myocardial Infarction
Background and hypothesis: RAGE and its ligands have been implicated in pathogenesis of ischemia/reperfusion injury. We hypothesized that RAGE expression in ischemic myocardium can be imaged in mice using Tc-99m labeled anti-RAGE monoclonal F(ab')2.
Methods: 11 C57BL/6 (WT) mice and 2 RAGE−/− mice underwent LAD ligation, 3 WT mice underwent sham surgery. At 24 to 48 hr after LAD ligation mice were injected with 0.53 mCi Tc-99m anti-RAGE F(ab')2 and 4–6 hr later (blood pool clearance) were injected with 0.15–0.2 mCi Tl-201 and immediately underwent dual isotope SPECT imaging on a micro-SPECT/CT scanner (Bioscan). At completion of imaging the heart was removed, counted, and sectioned for histology for Movat's trichrome, RAGE, 4-HNE (for oxidative stress), and MPO (for neutrophils).
Results: Uptake of radiolabeled antibody was seen in infarct zone on SPECT images in all 11 WT mice. No uptake was seen in the heart in the RAGE−/− mice or in the sham operated mice. Mean uptake of tracer in the infarct was 7.51 ± 6.2 × 10−3 %ID. Infarct sizes averaged 13.2%. Serial sections showed RAGE and MPO staining corresponding to infarct zone and averaging 11.8 % and 9.4 % myocardium respectively. 4-HNE staining was more extensive averaging 24%. One animal was injected with dual radiolabel and fluorescent labeled antibody. Fluorescence localized to the infarct zone.
Conclusions: RAGE expression in the ischemic zone of small myocardial infarctions in mice can be imaged in-vivo and is associated with markers for inflammation and oxidative stress.
- © 2010 by American Heart Association, Inc.