Abstract 3024: Sensitivity of Molecular MRI for Low Levels of Cardiomyocyte Apoptosis in an In-Vivo Model of Dilated Cardiomyopathy
Background: Cardiomyocyte (CM) apoptosis has been successfully imaged in-vivo by MRI in acutely injured myocardium. However, significantly lower levels of CM apoptosis are seen in dilated cardiomyopathy. The aim of this study was thus to image low levels of CM apoptosis, with the targeted nanoparticle AnxCLIO-Cy5.5 in the setting of chronic myocardial injury.
Methods: Transgenic mice with over-expression of the Gaq receptor were studied. These mice develop a postpartum cardiomyopathy characterized by apoptosis of 1–2% of CMs. The mice were injected 1–2 weeks postpartum with either active (AnxCLIO-Cy5.5, n = 5) or control (CLIO-Cy5.5, n = 5) probe at 10mg Fe/kg. T2* weighted MR images were then acquired in-vivo at 9.4 Tesla 48 hours later. MRI and fluorescence reflectance imaging were also performed in a further 6 mice given a dose of 3mg Fe/kg of either the active (n = 3) or control probe (n = 3).
Results: Biventricular dilatation and hypokinesis were seen in all mice. In addition, patchy foci of intramyocardial signal loss were seen in the MR images of those mice given the active probe at 10 mg Fe/kg (Figure 1a⇓) but not in those given the control probe (Figure 1B⇓). Fluorescence intensity was significantly higher (8.3 +/− 0.5 versus 6.4 +/− 0.2, p < 0.05) in the mice given the active probe (Figure 1c⇓) than in those given the control probe (Figure 1d⇓).
Conclusions: The targeted nanoparticle, AnxCLIO-Cy5.5, was able to cross the intact capillary membrane and image low levels of cardiomyocyte apoptosis in-vivo, by MRI, at a dose of 10 mg Fe/kg. This probe thus has the potential to provide valuable insights into the biology of heart failure and guide the development of novel therapies.