Comparison of a New 68Ga-Radiolabelled PET Imaging Agent sCD146 and RGD Peptide for In Vivo Evaluation of Angiogenesis in Mouse Model of Myocardial Infarction

Abstract

Ischemic vascular diseases are associated with elevated tissue expression of angiomotin (AMOT), a promising molecular target for PET imaging. On that basis, we developed an AMOT-targeting radiotracer, ⁶⁸Ga-sCD146 and performed the first in vivo evaluation on a myocardial infarction mice model and then, compared AMOT expression and α_vβ₃-integrin expression with ⁶⁸Ga-sCD146 and ⁶⁸Ga-RGD₂ imaging. After myocardial infarction (MI) induced by permanent ligation of the left anterior descending coronary artery, myocardial perfusion was evaluated by Doppler ultrasound and by ¹⁸F-FDG PET imaging. ⁶⁸Ga-sCD146 and ⁶⁸Ga-RGD₂ PET imaging were performed. In myocardial infarction model, heart-to-muscle ratio of ⁶⁸Ga-sCD146 imaging showed a significantly higher radiotracer uptake in the infarcted area of MI animals than in sham (* p = 0.04). Interestingly, we also observed significant correlations between ⁶⁸Ga-sCD146 imaging and delayed residual perfusion assessed by ¹⁸F-FDG (* p = 0.04), with lowest tissue fibrosis assessed by histological staining (* p = 0.04) and with functional recovery assessed by ultrasound imaging (** p = 0.01). ⁶⁸Ga-sCD146 demonstrated an increase in AMOT expression after MI. Altogether, significant correlations of early post-ischemic ⁶⁸Ga-sCD146 uptake with late heart perfusion, lower tissue fibrosis and better functional recovery, make ⁶⁸Ga-sCD146 a promising radiotracer for tissue angiogenesis assessment after MI.

Keywords: angiogenesis; angiomotin; gallium; myocardial infarction; sCD146.