Send to

Choose Destination
Bioorg Med Chem. 2008 Apr 15;16(8):4242-51. doi: 10.1016/j.bmc.2008.02.081. Epub 2008 Feb 29.

Formation of fluorine-18 labeled diaryl ureas--labeled VEGFR-2/PDGFR dual inhibitors as molecular imaging agents for angiogenesis.

Author information

Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University Hospital, Jerusalem 91120, Israel.


Urea subunits are common components of various pharmaceuticals' core structure. Since in most cases the design and development of PET biomarkers is based on approved or potential drugs, there is a growing need for a general labeling methodology of urea-containing pharmacophores. As a part of research in the field of molecular imaging of angiogenic processes, we synthesized several highly potent VEGFR-2/PDGFR dual inhibitors as potential PET biomarkers. The structure of these inhibitors is based on the N-phenyl-N'-{4-(4-quinolyloxy)phenyl}urea skeleton. A representative inhibitor was successfully labeled with fluorine-18 by a three-step process. Initially, a two-step radiosynthesis of 4-[(18)F]fluoro-aniline from 1,4-dinitrobenzene (60min, EOB decay corrected yield: 63%) was performed. At the third and final step, the 4-[(18)F]fluoro-aniline synthon reacted for 30min at room temperature with 4-(2-fluoro-4-isocyanato-phenoxy)-6,7-dimethoxy-quinoline to give complete conversion of the labeled synthon to 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-3-(4-[(18)F]fluoro-phenyl)-urea. The desired labeled product was obtained after total radiosynthesis time of 3h including HPLC purification with 46+/-1% EOB decay corrected radiochemical yield, 99% radiochemical purity, 99% chemical purity, and a specific activity of 400+/-37GBq/mmol (n=5).

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center