Targeted imaging of hypoxia-induced integrin activation in myocardium early after infarction
Targeted imaging of hypoxia-induced integrin activation in myocardium early after infarction
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DOI：
10.1152/japplphysiol.00861.2007
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发表时间：
2008-05-01
影响因子：
3.3
通讯作者：
Sinusas, Albert J.
中科院分区：
文献类型：
--
作者：
Kalinowski, Leszek;Dobrucki, Lawrence W.;Sinusas, Albert J.
α v β 3-整联蛋白在缺氧时在血管生成血管中表达，代表了心肌血管生成成像的潜在新靶点。本研究评估了无创性追踪心肌内缺氧诱导的α v β 3整合素激活作为心肌梗死后早期血管生成标志物的可行性。在啮齿动物和犬类研究中，冠状动脉闭塞会导致急性心肌梗死。一种新的In-111标记的放射性示踪剂靶向α v β 3-整联蛋白（In-111-RP 748）被用来定位缺氧诱导的血管生成区域梗死后早期。在啮齿动物研究中，用阴性对照化合物（In-111-RP 790）证实了In-111-RP 748对α v β 3-整联蛋白的特异性，这些化合物的局部摄取与Tl-201灌注和（99）mTc标记的硝基咪唑（BRU 59 -21）相关，后者用作心肌缺氧的定量标志物。离体分析表明，只有In-111-RP 748被选择性地保留在具有减少的Tl-201灌注的梗塞区域中，并且与BRU 59 -21的摄取相关。在犬研究中，使用体内单光子发射计算机断层扫描（SPECT）、离体平面成像和心肌组织的γ井计数评估了In-111-RP 748的心肌摄取，并与（99）mTc标记的2-甲氧基-2-甲基异丙基腈（99 mTc-sestamibi）灌注相关。In-111-RP 748和（99）mTc-司他米比的双放射性示踪剂体内SPECT成像提供了梗塞区域内In-111-RP 748摄取的可视化，这通过切除的心肌切片的离体平面成像证实。心肌In-111-RP 748滞留与梗死区域α v β 3-整合素表达/激活的组织学证据相关。In-111-RP 748成像为评价梗死后早期心肌中缺氧诱导的α v β 3整合素激活提供了一种新的非侵入性方法，并可能被证明可用于指导和评价缺血性心脏病患者的血管生成治疗。
The alpha v beta 3-integrin is expressed in angiogenic vessels in response to hypoxia and represents a potential novel target for imaging myocardial angiogenesis. This study evaluated the feasibility of noninvasively tracking hypoxiainduced alpha v beta 3-integrin activation within the myocardium as a marker of angiogenesis early after myocardial infarction. Acute myocardial infarction was produced by coronary artery occlusion in rodent and canine studies. A novel In-111-labeled radiotracer targeted at the alpha v beta 3-integrin (In-111-RP748) was used to localize regions of hypoxiainduced angiogenesis early after infarction. In rodent studies, the specificity of In-111-RP748 for alpha v beta 3-integrin was confirmed with a negative control compound (In-111- RP790), and regional uptake of these compounds correlated with Tl-201 perfusion and a (99)mTc-labeled nitroimidazole (BRU59-21), which was used as a quantitative marker of myocardial hypoxia. The ex vivo analysis demonstrated that only In-111-RP748 was selectively retained in infarcted regions with reduced Tl-201 perfusion and correlated with uptake of BRU59-21. In canine studies, myocardial uptake of In-111-RP748 was assessed using in vivo single-photon-emission computed tomography (SPECT), ex vivo planar imaging, and gamma well counting of myocardial tissue and correlated with (99)mTc-labeled 2-methoxy-2-methyl-propylisonitrile (99mTc-sestamibi) perfusion. Dual-radiotracer in vivo SPECT imaging of In-111- RP748 and (99)mTc-sestamibi provided visualization of In-111- RP748 uptake within the infarct region, which was confirmed by ex vivo planar imaging of excised myocardial slices. Myocardial In-111- RP748 retention was associated with histological evidence of alpha v beta 3-integrin expression/ activation in the infarct region. In-111- RP748 imaging provides a novel noninvasive approach for evaluation of hypoxia-induced alpha v beta 3-integrin activation in myocardium early after infarction and may prove useful for directing and evaluating angiogenic therapies in patients with ischemic heart disease.