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

Abstract

SUMMARYLeft 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), an 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 111 In Fab fragment of a monoclonal antibody specific for TNC.111 In-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 performed autoradiography and dual-isotope single-photon emission computed tomography imaging (SPECT) of 111 In-anti-TNC-Fab and 99mTc 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 111 In-anti-TNC-Fab, which was complementary to the perfusion image.The results of the present study indicated that we can localize the infarcted region in the heart by ex vivo and in vivo imaging methods using 111 In-anti-TNC-Fab, and suggested the potential usefulness of noninvasive detection of cardiac repair. (Int Heart J 2008; From the

High prevalence of chronic myocarditis in dilated cardiomyopathy referred for left ventriculoplasty: expression of tenascin C as a possible marker for inflammation

“…Trial of immunoscintigraphy with antimyosin antibodies has been conducted to diagnose myocardial damage [32]. Using In-111-labeled anti-TNC antibody, we have succeeded in in vivo imaging of inflammatory lesion of rat myocarditis [33] and myocardial infarction model [34]. Molecular imaging using anti-TNC antibody could be exploited to detect active inflammatory lesion in DCM patients.…”

Dynamic Expression of Tenascin-C After Myocardial Ischemia and Reperfusion: Assessment by 125I-Anti–Tenascin-C Antibody Imaging

“…Labeling with 123 I can easily be performed in the same way as for 125 I, and 111 In labeling has already been achieved (9,17). Rapid blood clearance and retention of 125 I-TNC-Ab in the infarcted area, resulting in a decent target-to-blood ratio and good target-to-lung ratio, indicate the feasibility of in vivo imaging at 5 h or later after tracer injection.…”

“…In previous animal studies on acute myocardial infarction induced by permanent ligation of a coronary artery, it was reported that tenascin-C appears transiently during the acute stage, plays several significant roles in myocardial tissue remodeling, and may be a potential candidate for molecular imaging (9,17). For clinical application of the imaging, it is essential to analyze the molecular dynamics in the model of myocardial ischemia and reperfusion that is the general scenario in the era of percutaneous coronary intervention in acute coronary syndrome.…”

New radiotracers for imaging of vascular targets in angiogenesis-related diseases

“…Due to the vital role of TNC in cardiac and arterial injury, radiolabeled anti-TNC antibodies were chosen for detection of cardiac or arterial diseases such as autoimmune myocarditis [198], MI [199], or cardiac repair after acute MI [200]. Due to the invasiveness and inferior sensitivity of biopsy test in myocarditis diagnosis, a new diagnostic technique was developed in 2002 for the early detection of myocarditis using TNC as a molecular marker [198].…”

“…After administering of 111 In-4F10 into a rat model of acute MI, significantly radioactivity accumulation was observed at the infarcted myocardium than the non-infarcted. Following similar strategy, cardiac repair evaluation was carried out at the early stage of left ventricular remodeling using an 111 In-anti-TNC-Fab, generated from a mAb for TNC [200]. Autoradiography and dual-isotope SPECT were performed with both 111 In-anti-TNC-Fab and 99m Tc-MIBI.…”