title: Radiosynthesis of [13N]dantrolene, a positron emission tomography probe for breast cancer resistant protein, using no-carrier-added [13N]ammonia.
abstract: Dantrolene (1) is a substrate for breast cancer resistant protein, which is widely distributed in the blood-brain-barrier, intestine, gall bladder, and liver. PET study with 1 labeled with a positron emitter can be used to visualize BCRP and to elucidate the effect of BCRP on the pharmacokinetics of drugs. The objective of this study was to label 1 using nitrogen-13 ((13)N, a positron emitter; half-life: 9.9min). Using no-carrier-added [(13)N]NH(3) as the labeling agent, we synthesized [(13)N]dantrolene ([(13)N]1) for the first time. The reaction of carbomyl chloride 2b with [(13)N]NH(3) gave an unsymmetrical urea [(13)N]3, followed by cyclization of [(13)N]3 to afford [(13)N]1. Due to its instability, 2b was prepared in situ by treating amine 5 with triphosgene in a ratio of 4 to 1 and used for subsequent [(13)N]ammonolysis without purification.
authors: Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors: Katsushi
authors: K
authors: Kumata
authors: Masanao
authors: M
authors: Ogawa
authors: Makoto
authors: M
authors: Takei
authors: Masayuki
authors: M
authors: Fujinaga
authors: Yuichiro
authors: Y
authors: Yoshida
authors: Nobuki
authors: N
authors: Nengaki
authors: Toshimitsu
authors: T
authors: Fukumura
authors: Kazutoshi
authors: K
authors: Suzuki
authors: Ming-Rong
authors: MR
authors: Zhang
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000378:metabolism; D000641:Ammonia / Q000737:chemistry*; D001812:Blood-Brain Barrier; D001943:Breast Neoplasms / Q000000981:diagnostic imaging*; D003500:Cyclization; D003620:Dantrolene / Q000138:chemical synthesis / Q000737:chemistry*; D005260:Female; D006801:Humans; D007553:Isotope Labeling; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000378:metabolism; D009590:Nitrogen Radioisotopes / Q000737:chemistry; D010705:Phosgene / Q000031:analogs & derivatives / Q000737:chemistry; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry*; D014508:Urea / Q000737:chemistry
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins; D009590:Nitrogen Radioisotopes; D019275:Radiopharmaceuticals; D010705:Phosgene; C111044:bis(trichloromethyl) carbonate; D000641:Ammonia; D014508:Urea; D003620:Dantrolene