期刊
CIRCULATION
卷 112, 期 20, 页码 3157-3167出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCULATIONAHA.105.583021
关键词
myocardial infarction; metalloproteinases; remodeling; radionuclide imaging
资金
- NHLBI NIH HHS [P01-HL-48788, R01 HL078650, R01-HL-65662, R01 HL078650-04, R01-HL-59165] Funding Source: Medline
Background: Time-dependent activation of matrix metalloproteinases (MMPs) after myocardial infarction (MI) contributes to adverse left ventricular (LV) remodeling; however, noninvasive methods to monitor this process serially are needed. Methods and Results: MMP-targeted radiotracers were developed that displayed selective binding kinetics to the active MMP catalytic domain. Initial nonimaging studies were performed with a In-111-labeled MMP-targeted radiotracer (In-111-RP782) and negative control compound (In-111-RP788) in control mice (Ctrl) and in mice 1 week after surgically induced MI. Localization of In-111-RP782 was demonstrated within the MI by microautoradiography. A 334 +/- 44% increase (P < 0.001 versus Ctrl) in relative retention of In-111-RP782 was confirmed by gamma well counting of myocardium. Subsequent high-resolution dual-isotope planar and hybrid micro-single-photon emission computed tomography/CT imaging studies with an analogous Tc-99m-labeled MMP-targeted radiotracer (Tc-99m-RP805) and Tl-201 demonstrated favorable biodistribution and clearance kinetics of Tc-99m-RP805 for in vivo cardiac imaging, with robust retention 1 to 3 weeks after MI in regions of decreased 201Tl perfusion. Gamma well counting yielded a similar approximate to 300% increase in relative myocardial retention of Tc-99m-RP805 in MI regions (Ctrl, 102 +/- 9%; 1 week, 351 +/- 77%; 2 weeks, 291 +/- 45%; 3 weeks, 292 +/- 41%; P < 0.05 versus Ctrl). Myocardial uptake in the MI region was also significantly increased approximate to 5-fold when expressed as percentage injected dose per gram tissue. There was also a significant 2-fold increase in myocardial activity in remote regions relative to control mice, suggesting activation of MMPs in regions remote from the MI. Conclusions: This novel noninvasive targeted MMP radiotracer imaging approach holds significant diagnostic potential for in vivo localization of MMP activation and tracking of MMP-mediated post-MI remodeling.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据