Abstract 553: In vivo Targeted Molecular Imaging of Matrix Metalloproteinase Inhibition in Experimental Abdominal Aortic Aneurysm Disease
Introduction: Although therapies aimed at inhibiting MMP activity are effective in limiting experimental models of abdominal aortic aneurysm (AAA), the lack of a noninvasive modality to track real-time efficacy of these agents is what hinders their clinical application. We assessed the hypothesis that tracking the molecular activity of MMP inhibition will provide a marker for AAA response to therapy.
Methods: Apo E-deficient mice were infused with Angiotensin II (1000ng/kg/min) to create murine AAAs. Mice were divided into 3 groups (n = 3/group) for administration of the following by daily oral gavage:
Doxycycline (30mg/kg), and
Aortic diameter was measured by ultrasound and Fluorescence Molecular Tomography (FMT) imaging was performed at day 14 for in vivo MMP activity. Mice were imaged 48hrs after injection of near infrared activatable MMP probe (MMPSense 680, VisEn Medical Inc) and sacrificed for histological analysis of MMP-9 expression.
Results: The average diameter of Saline treated mice was significantly larger than Doxycycline and Fluvastatin treated mice (2.05 ± 0.26mm vs 1.16 ± 0.03mm and 1.27 ± 0.06mm, p < 0.05). FMT imaging demonstrated a higher signal intensity in Saline treated mice (1.73 ± 0.26pmoles) compared to Doxycycline (0.83 ± 0.09pmoles, p < 0.05) and Fluvastatin treated mice (0.73 ± 0.16pmoles, p < 0.05). Histology confirmed these results with comparable decreases in MMP expression (Figure⇓).
Conclusion: FMT imaging reflects the variance seen in MMP inhibition. Noninvasive imaging of MMP activity may serve as a surrogate end point for evaluation of novel therapies aimed against AAA progression.