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: [(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. CONCLUSION: 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.
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: [(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. CONCLUSION: 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.
Authors: C Willam; P Koehne; J S Jürgensen; M Gräfe; K D Wagner; S Bachmann; U Frei; K U Eckardt Journal: Circ Res Date: 2000-09-01 Impact factor: 17.367