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Application of Hybrid Matrix Metalloproteinase-Targeted and Dynamic 201Tl Single-Photon Emission Computed Tomography/Computed Tomography Imaging for Evaluation of Early Post-Myocardial Infarction Remodeling.


ABSTRACT: BACKGROUND:The induction of matrix metalloproteinases (MMPs) and reduction in tissue inhibitors of MMPs (TIMPs) plays a role in ischemia/reperfusion (I/R) injury post-myocardial infarction (MI) and subsequent left ventricular remodeling. We developed a hybrid dual isotope single-photon emission computed tomography/computed tomography approach for noninvasive evaluation of regional myocardial MMP activation with 99mTc-RP805 and dynamic 201Tl for determination of myocardial blood flow, to quantify the effects of intracoronary delivery of recombinant TIMP-3 (rTIMP-3) on I/R injury. METHODS:Studies were performed in control pigs (n=5) and pigs following 90-minute balloon occlusion-induced ischemia/reperfusion (I/R) of left anterior descending artery (n=9). Before reperfusion, pigs with I/R were randomly assigned to intracoronary infusion of rTIMP-3 (1.0 mg/kg; n=5) or saline (n=4). Three days post-I/R, dual isotope imaging was performed with 99mTc-RP805 and 201Tl along with contrast cineCT to assess left ventricular function. RESULTS:The ischemic to nonischemic ratio of 99mTc-RP805 was significantly increased following I/R in saline group (4.03±1.40), and this ratio was significantly reduced with rTIMP-3 treatment (2.22±0.57; P=0.03). This reduction in MMP activity in the MI-rTIMP-3 treatment group was associated with an improvement in relative MI region myocardial blood flow compared with the MI-saline group and improved myocardial strain in the MI region. CONCLUSIONS:We have established a novel hybrid single-photon emission computed tomography/computed tomography imaging approach for the quantitative assessment of regional MMP activation, myocardial blood flow, and cardiac function post-I/R that can be used to evaluate therapeutic interventions such as intracoronary delivery of rTIMP-3 for reduction of I/R injury in the early phases of post-MI remodeling.

SUBMITTER: Thorn SL 

PROVIDER: S-EPMC7250243 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Application of Hybrid Matrix Metalloproteinase-Targeted and Dynamic <sup>201</sup>Tl Single-Photon Emission Computed Tomography/Computed Tomography Imaging for Evaluation of Early Post-Myocardial Infarction Remodeling.

Thorn Stephanie L SL   Barlow Shayne C SC   Feher Attila A   Stacy Mitchel R MR   Doviak Heather H   Jacobs Julia J   Zellars Kia K   Renaud Jennifer M JM   Klein Ran R   deKemp Robert A RA   Khakoo Aarif Y AY   Lee TaeWeon T   Spinale Francis G FG   Sinusas Albert J AJ  

Circulation. Cardiovascular imaging 20191111 11


<h4>Background</h4>The induction of matrix metalloproteinases (MMPs) and reduction in tissue inhibitors of MMPs (TIMPs) plays a role in ischemia/reperfusion (I/R) injury post-myocardial infarction (MI) and subsequent left ventricular remodeling. We developed a hybrid dual isotope single-photon emission computed tomography/computed tomography approach for noninvasive evaluation of regional myocardial MMP activation with <sup>99m</sup>Tc-RP805 and dynamic <sup>201</sup>Tl for determination of myoc  ...[more]

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