title: Synthesis and biological evaluation of a fluorine-18 derivative of dasatinib.
abstract: Tyrosine kinases often play pivotal roles in the pathogenesis of cancer and are good candidates for therapeutic intervention and targeted molecular imaging. The precursor synthesis, radiosynthesis, and biological characterization of a fluorine-18 analog of dasatinib, a multitargeted kinase inhibitor, are reported. Compound 5 potently inhibits Abl, Src, and Kit kinases and inhibits K562 and M07e/p210bcr-abl human leukemic cell growth. Using positron emission tomography, we visualized K562 tumor xenografts in mice with [18F]-5.
authors.affiliation: Department of Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
authors.forename: Darren R
authors.initials: DR
authors.lastname: Veach
authors.forename: Mohammad
authors.initials: M
authors.lastname: Namavari
authors.forename: Nagavarakishore
authors.initials: N
authors.lastname: Pillarsetty
authors.forename: Elmer B
authors.initials: EB
authors.lastname: Santos
authors.forename: Tatiana
authors.initials: T
authors.lastname: Beresten-Kochetkov
authors.forename: Caryl
authors.initials: C
authors.lastname: Lambek
authors.forename: Blesida J
authors.initials: BJ
authors.lastname: Punzalan
authors.forename: Christophe
authors.initials: C
authors.lastname: Antczak
authors.forename: Peter M
authors.initials: PM
authors.lastname: Smith-Jones
authors.forename: Hakim
authors.initials: H
authors.lastname: Djaballah
authors.forename: Bayard
authors.initials: B
authors.lastname: Clarkson
authors.forename: Steven M
authors.initials: SM
authors.lastname: Larson
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000069439:Dasatinib; D005462:Fluorine Radioisotopes; D016044:Fusion Proteins, bcr-abl; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D049268:Positron-Emission Tomography; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D013844:Thiazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D014183:Transplantation, Heterologous; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
chemical_list: D005462:Fluorine Radioisotopes; D011743:Pyrimidines; D019275:Radiopharmaceuticals; D013844:Thiazoles; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; D016044:Fusion Proteins, bcr-abl; D019061:src-Family Kinases; D000069439:Dasatinib