Successful inflammation imaging of non-human primate hearts using an antibody specific for Tenascin-C

Abstract

Inflammation after myocardial infarction (MI) may be a major factor influencing ventricular remodeling, leading to congestive heart failure and arrhythmia. Therefore, inflammation in the heart needs to be monitored. Tenascin-C (TNC) is an extracellular matrix molecule not normally expressed, but it is strongly upregulated when associated with active inflammation. Based on this characteristic, we successfully imaged in vivo inflammatory lesions in rat models using 111 Indium ( 111 In)-labeled anti-TNC antibodies. The aim of the present study was to further assess the applicability of this molecular imaging probe to detect inflammatory activity in primate hearts. We generated an MI model of cynomolgus monkeys (Macaca fascicularis) by coronary artery ligation and performed dual-isotope single-photon emission computed tomography (SPECT) imaging with an 111 In-labeled anti-TNC antibody Fab’ fragment ( 111 In-TNC Fab’) and 99m technetium methoxy-isobutyl isonitrile ( 99m Tc-MIBI). Dual autoradiography was used to compare the uptake of 111 In-TNC Fab’ with histology and immunostaining for TNC. Dual-isotope SPECT showed the regional myocardial uptake of 111 In-TNC Fab’ complementary to a defect in the perfusion image by 99m Tc-MIBI. The high radioactivity of 111 In-TNC Fab’ by autoradiography corresponded to immunostaining for TNC, which was observed in inflammatory lesions at the border zone between the infarcted and non-infarcted areas of the left ventricle and at the epi/pericarditis lesions of the right ventricle. These results demonstrate the potential of 111 In-TNC-Fab’ imaging to monitor myocardial injury and inflammation and suggest the feasibility of the non-invasive detection of cardiac inflammation following acute MI in a preclinical stage before testing in humans.