Synthesis and preliminary evaluation of cardiac imaging with [68Ga]Ga-NOTA-CTP in normal and infarcted CD1 mice†

Abstract

Cell-penetrating peptide-based probes for positron emission tomography (PET) are currently being developed for cardiac imaging. Herein, we have conjugated a synthetic 12 amino acids (NH₂-APWHLSSQYSRT-COOH) cardiac targeting peptide (CTP) with a NOTA chelator for ⁶⁸Ga labeling. The [⁶⁸Ga]Ga-NOTA-CTP was synthesized with a decay-corrected radiochemical yield of 68.9 ± 12.8% (n = 13) and molar activity (A_m) of 1.3 ± 0.5 GBq per μmol (n = 13). The tracer was evaluated in healthy and diseased CD1 mice with myocardial infarction following ligation of the left anterior descending artery. PET/CT imaging and ex vivo biodistribution revealed rapid (within 30 min) clearance of [⁶⁸Ga]Ga-NOTA-CTP from the blood through renal and hepatobiliary excretion pathways in both healthy and infarcted animals. The uptake of [⁶⁸Ga]Ga-NOTA-CTP in the heart of healthy and infarcted animals did not show any statistically significant difference for up to 120 min post-injection, but regional differences within healthy and infarcted hearts were detected with [⁶⁸Ga]Ga-NOTA-CTP by PET/CT imaging at early time points post-injection. Within a healthy heart, the left ventricle standardized uptake value (SUV) was lower than the right ventricle SUV at 10–30 min post-injection. This regional difference between the left and right ventricles was absent in the infarcted heart, likely due to post-ligation changes.