Successful Inflammation Imaging of Non-Human Primate Hearts Using an Antibody Specific for Tenascin-C

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 ¹¹¹Indium (¹¹¹In)-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 ¹¹¹In-labeled anti-TNC antibody Fab' fragment (¹¹¹In-TNC Fab') and ^99mtechnetium methoxy-isobutyl isonitrile (^99mTc-MIBI). Dual autoradiography was used to compare the uptake of ¹¹¹In-TNC Fab' with histology and immunostaining for TNC. Dual-isotope SPECT showed the regional myocardial uptake of ¹¹¹In-TNC Fab' complementary to a defect in the perfusion image by ^99mTc-MIBI. The high radioactivity of ¹¹¹In-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 ¹¹¹In-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.