Published in:
01-04-2015 | Research Article
PET Molecular Imaging of Angiogenesis with a Multiple Tyrosine Kinase Receptor-Targeted Agent in a Rat Model of Myocardial Infarction
Authors:
Samar Dissoki, Galith Abourbeh, Olga Salnikov, Eyal Mishani, Orit Jacobson
Published in:
Molecular Imaging and Biology
|
Issue 2/2015
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Abstract
Purpose
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.
Procedures
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
[11C]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, [11C]ATV-1 uptake in the LV significantly correlated with Tie-2, VEGFR-2, and PDGFRα expression.
Conclusion
Imaging angiogenesis in MI rats using [11C]ATV-1 and PET has been demonstrated. These results merit further research and development of more hydrophilic modified [11C]ATV-1 as a PET tracer.