PET molecular imaging of angiogenesis with a multiple tyrosine kinase receptor-targeted agent in a rat model of myocardial infarction.
Kata kunci
Abstrak
OBJECTIVE
Angiogenesis plays a major role in tissue remodeling and repair after myocardial infarction (MI), and imaging it could provide information on the healing process. During angiogenesis, vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors (PDGFRs), and Tie receptors are upregulated, and this study aimed to develop a C-11 positron emission tomography (PET) agent for imaging angiogenesis by targeting these receptors.
METHODS
A VEGFR-2/Tie-2/PDGFRα inhibitor (N-(6-{4-[3-(2-fluoro-5-trifluoromethyl-phenyl)-ureido]-phenoxy}-1H-benzoimidazol-2-yl)-2-(4-methyl-piperazin-1-yl)-acetamide (ATV-1)) was synthesized and labeled with C-11. MicroPET imaging of a rat MI model was compared to proteins expression by immunohistochemistry.
RESULTS
[(11)C]ATV-1 specifically accumulated in the infracted region of the left ventricular (LV) lateral wall more than in the interventricular septal wall, but not in sham-operated or healthy animals. Moreover, [(11)C]ATV-1 uptake in the LV significantly correlated with Tie-2, VEGFR-2, and PDGFRα expression.
CONCLUSIONS
Imaging angiogenesis in MI rats using [(11)C]ATV-1 and PET has been demonstrated. These results merit further research and development of more hydrophilic modified [(11)C]ATV-1 as a PET tracer.
