title: [11C]sorafenib: radiosynthesis and preliminary PET study of brain uptake in P-gp/Bcrp knockout mice.
abstract: Sorafenib (Nexavar, BAY43-9006, 1) is a second-generation, orally active multikinase inhibitor that is approved for the treatment of some cancers in patients. In this Letter, we developed [(11)C]1 as a novel positron emission tomography (PET) probe, and evaluated the influence of ABC transporters-mediated efflux on brain uptake using PET with [(11)C]1 in P-glycoprotein (P-gp)/breast cancer resistance protein (Bcrp) knockout mice versus wild-type mice. [(11)C]1 was synthesized by the reaction of hydrochloride of aniline 2 with [(11)C]phosgene ([(11)C]COCl(2)) to give isocyanate [(11)C]6, followed by reaction with another aniline 3. Small-animal PET study with [(11)C]1 indicated that the radioactivity level (AUC(0-60 min), SUV×min) in the brains of P-gp/Bcrp knockout mice was about three times higher than in wild-type mice.
authors.affiliation: Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Asakawa
authors.forename: Masanao
authors.initials: M
authors.lastname: Ogawa
authors.forename: Katsushi
authors.initials: K
authors.lastname: Kumata
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujinaga
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato
authors.forename: Tomoteru
authors.initials: T
authors.lastname: Yamasaki
authors.forename: Joji
authors.initials: J
authors.lastname: Yui
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kawamura
authors.forename: Akiko
authors.initials: A
authors.lastname: Hatori
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Fukumura
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001557:Benzenesulfonates / Q000138:chemical synthesis / Q000737:chemistry*; D001921:Brain / Q000000981:diagnostic imaging*; D002250:Carbon Radioisotopes / Q000737:chemistry; D051379:Mice; D018345:Mice, Knockout; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry*; D000077157:Sorafenib
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C501412:Abcg2 protein, mouse; D001557:Benzenesulfonates; D002250:Carbon Radioisotopes; D010671:Phenylurea Compounds; D011725:Pyridines; D019275:Radiopharmaceuticals; D009536:Niacinamide; D000077157:Sorafenib