Noninvasive Detection of Cardiac Repair After Acute Myocardial Infarction in Rats by 111In Fab Fragment of Monoclonal Antibody Specific for Tenascin-C

Noninvasive Detection of Cardiac Repair After Acute Myocardial Infarction in Rats by 111In Fab Fragment of Monoclonal Antibody Specific for Tenascin-C
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DOI:
10.1536/ihj.49.481
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发表时间:
2008-07-01
影响因子:
1.5
通讯作者:
Komuro, Issei
Komuro, Issei
中科院分区:
医学4区
文献类型:
--
作者:
Odaka, Kenichi;Uehara, Tomoya;Komuro, Issei

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急性心肌梗死(MI)后左室(LV)重构可引起心力衰竭,因此作为左室重构的早期阶段评估心脏修复具有重要意义。Tenascin-C (TNC)是一种细胞外基质糖蛋白,在心肌梗死后组织重构的早期阶段,在心脏中有短暂而丰富的表达,但在健康成人心脏中不表达。本研究旨在开发一种新的无创诊断技术来检测急性心肌梗死后的心脏修复。TNC特异性单克隆抗体In-111 Fab片段。在心肌梗死发生后1 (D1, n= 3)、3 (D3, n= 5)、5 (D5, n= 5)天及5只假手术大鼠(S)静脉注射in -111-anti- tnc - fab。我们对In-111-anti-TNC-Fab和Tc-99m甲氧基异丁基异腈(MIBI)进行了放射自显像和双同位素单光子发射计算机断层扫描成像(SPECT)。D组心脏放射性明显高于S组(D1 0.45 +/- 0.06%注射剂量/g; D3 0.64 +/- 0.12; D5 0.38 +/- 0.07) (D1、D3 0.27 +/- 0.06,与D1、D3比较P < 0.01,与D5比较P < 0.05)。通过放射自显像,心肌梗死区比非梗死区有更高的放射性。双同位素SPECT显示局部心肌摄取In-111-anti-TNC-Fab,这与灌注图像是互补的。本研究结果表明,通过in -111-anti- tnc - fab的体外和体内成像方法,我们可以定位心脏梗死区域,并提示无创检测心脏修复的潜在用途。[J] .中华心脏杂志,2008;49:481-492。
Left ventricular (LV) remodeling after acute myocardial infarction (MI) causes heart failure, and thus it is important to evaluate cardiac repair as the early stage of LV remodeling. Tenascin-C (TNC), all extracellular matrix glycoprotein, is transiently and abundantly expressed in the heart during the early stage of tissue remodeling after MI. However, it is not expressed in healthy adult heart. This study was undertaken to develop a new noninvasive diagnostic technique to detect cardiac repair after acute MI using. In-111 Fab fragment of a monoclonal antibody specific for TNC.In-111-anti-TNC-Fab was injected intravenously in 13 rats at 1 (D1, n = 3) 3 (D3, n= 5), and 5 (D5, n = 5) days after producing MI and in 5 sham-operated rats (S). We per-formed autoradiography and dual-isotope single-photon emission computed tomography imaging (SPECT) of In-111-anti-TNC-Fab and Tc-99m methoxyisobutyl isonitrile (MIBI).The radioactivity in the heart was significantly higher in D (D1 0.45 +/- 0.06% injected-dose/g; D3, 0.64 +/- 0.12; D5, 0.38 +/- 0.07) than S (0.27 +/- 0.06, P < 0.01 versus D1 and D3, P < 0.05 versus D5). By autoradiography, higher radioactivities were observed in the infarcted area than in the noninfarcted area of MI hearts. Dual-isotope SPECT demonstrated the regional myocardial uptake of In-111-anti-TNC-Fab, which was complementary to the perfusion image.The results of the present study indicated that we call localize the infarcted region ill the heart by ex vivo and in vivo imaging methods using In-111-anti-TNC-Fab, and suggested the potential usefulness of noninvasive detection of cardiac repair. (Int Heart J 2008; 49: 481-492).