Fluorine-18-Radiolabeling and Radiopharmacological Characterization of a Benzodioxolylpyrimidine as a Radiotracer Targeting the Receptor Tyrosine Kinase EphB4

Members of the Eph receptor tyrosine kinase family play essential roles in the pathogenesis of cancer and, therefore, are promising candidates for molecular imaging purposes, e.g. by positron emission tomography (PET). In this regard, radiochemical access to novel PET radiotracers derived from potent inhibitors targeting EphB4 kinase domain and bearing the benzodioxolylpyrimidine structural motif was developed. In order to obtain a fluorine-18-radiolabeled tracer, the respective tosylated precursor was prepared. Due to the implication of EphB4, particularly, in melanoma progression, angiogenesis, and metastasis, EphB4 overexpressing human melanoma cells were used as an in vitro model for radiopharmacological evaluation of the radiotracer. Furthermore, NMRI nu/nu mice bearing both EphB4 overexpressing tumors and control tumors were used for radiopharmacological characterization by biodistribution studies ex vivo and dynamic small animal PET experiments in vivo.