title: New radiosynthesis of 2-deoxy-2-[(18)F]fluoroacetamido-D-glucopyranose and its evaluation as a bacterial infections imaging agent.
abstract: BACKGROUND
  The diagnosis of infection and the ability to distinguish bacterial infection from nonbacterial inflammation by positron emission tomography (PET) have gained interest in recent years, but still few specific radiopharmaceuticals are available for use. In this study, we developed a new radiosynthesis method of 2-deoxy-2-[(18)F]fluoroacetamido-d-glucopyranose ([(18)F]FAG) by applying microwave irradiation and demonstrated that [(18)F]FAG could be a potential radiopharmaceutical to distinguish bacterial infection from nonbacterial inflammation.
  
  
  METHODS
  1,3,4,6-Tetra-O-acetyl-2-deoxy-2-bromoacetamido-d-glucopyranose was used as precursor, and labeling was performed under microwave irradiation conditions followed by alkaline hydrolysis and high-performance liquid chromatography (HPLC) purification. In vitro uptake of [(18)F]FAG by Escherichia coli was performed. Tissue biodistribution of [(18)F]FAG was performed in mice. Moreover, PET imaging acquisition of E. coli infection and nonbacterial inflammation models was performed in rats. Tissue radiotracer-accumulated sites were analyzed by hematoxylin and eosin staining and anti-E.coli immunostaining.
  
  
  RESULTS
  The radiosynthesis of [(18)F]FAG was achieved with microwave irradiation, and the radiochemical yield was 9.7%±2.8% end of bombardment (EOB); the radiochemical purity was more than 98%, and the total synthesis time was 62 min. Compared with control group, in vitro uptake of [(18)F]FAG by E. coli was significantly decrease in inhibition group (P<.05). Biodistribution studies in mice showed rapid clearance of [(18)F]FAG from the animal body. [(18)F]FAG clearly visualized the infection areas but not nonbacterial inflammation areas in PET studies. Quantitative analysis revealed that the uptake of [(18)F]FAG into infection areas was significantly higher than that of [(18)F]FAG into inflammation areas (P<.05). Histological analysis demonstrated the presence of bacterial cells at the sites of accumulation of [(18)F]FAG.
  
  
  CONCLUSIONS
  Using 1,3,4,6-tetra-O-acetyl-2-deoxy-2-bromoacetamido-d-glucopyranose as a precursor, the new radiosynthesis method of [(18)F]FAG was achieved in fewer steps and with a shorter synthesis time than previously reported. Furthermore, [(18)F]FAG was able to distinguish bacterial infection from nonbacterial inflammation.
authors.affiliation: Biomedical Imaging Research Center, University of Fukui, Eiheiji, Yoshida, Fukui, 910-1193, Japan.
authors.forename: Miguel E
authors.initials: ME
authors.lastname: Martínez
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kiyono
authors.forename: Sakon
authors.initials: S
authors.lastname: Noriki
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Inai
authors.forename: Katheryn S
authors.initials: KS
authors.lastname: Mandap
authors.forename: Masato
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mori
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tokunaga
authors.forename: Vijay N
authors.initials: VN
authors.lastname: Tiwari
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Okazawa
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Fujibayashi
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Ido
mesh_terms: D000117:Acetylglucosamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001424:Bacterial Infections / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism; D001692:Biological Transport; D002475:Cellobiose / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D003937:Diagnosis, Differential; D004926:Escherichia coli / Q000378:metabolism / Q000472:pathogenicity; D007249:Inflammation / Q000175:diagnosis; D008297:Male; D051379:Mice; D008872:Microwaves; D049268:Positron-Emission Tomography; D011854:Radiochemistry / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats
chemical_list: C568677:2-deoxy-2-fluoroacetamidoglucopyranose; D019275:Radiopharmaceuticals; D002475:Cellobiose; D000117:Acetylglucosamine