Abstract 3164: A Matrix Metalloproteinase (MMP) Targeted Radiotracer Tracks Spatial Changes in Myocardial MMP-2 Activation Following Myocardial Infarction
Background: Increased matrix metalloproteinase (MMP) induction and activation is a critical pathophysiological event following myocardial infarction (MI). However, examining MMP activity post-MI has been restricted to indirect methods such as tissue sampling; problematic for clinical applications. The study tested the hypothesis that a 99mTc-labeled MMP targeted radiotracer would track spatial and temporal post-MI changes in MMP activity.
Methods/Results: The in vivo characteristics of a validated radiotracer (MMP tracer; 99mTc-RP805, Bristol-Myers Squibb) that binds to active MMP sites were compared to in situ thallium (201Tl) uptake and MMP-2 (zymography) in pigs at 1 (n = 5) and 2 (n = 5) weeks post-MI (circumflex ligation) and in controls (n = 5). Following MMP tracer and Tl infusions, the LV was sectioned along the short axis sections, and divided into endocardial (ENDO) and epicardial (EPI) regions. While Tl uptake was reduced by over 50% in the MI region (p < 0.05), MMP tracer uptake was increased within ENDO and EPI at 1 week post-MI (413 ± 63, 398 ± 57% respectively, p < 0.05) and remained increased at 2 weeks (484 ± 102, 371 ± 81%, p < 0.05). MMP-2 increased within the ENDO and EPI at 1 week (4926 ± 1976, 4341 ± 1678%, p < 0.05) and remained elevated at week 2 post-MI. Registration of LV sections localized MMP tracer uptake to regions of MMP-2 induction (Left) and the active form of MMP-2 (64kDa) was correlated to MMP tracer uptake (Right)
Conclusions: Intravenous delivery of a MMP targeted radiotracer identified sites of increased MMP-2 activation following MI, thereby providing a rational approach for in vivo imaging of the MMP system during post-MI LV remodeling.