title: Design of silicon-based misonidazole analogues and (18)F-radiolabelling.
abstract: BACKGROUND
  Development of new (18)F-labeled tracers for positron emission tomography (PET) imaging is increasingly important. Herein, we described the synthesis of silicon analogues of [(18)F]fluoromisonidazole in order to develop new radiolabelled compounds for the detection of tumour hypoxic domain. Their stabilities and their in vivo biodistribution were evaluated.
  
  
  METHODS
  (18)F-labeled silicon-based misonidazole analogues were synthesized by alkylating 2-nitroimidazole with alkyloxy-(3-chloropropyl)dialkyl or diarylsilane. These intermediates were labeled with [(18)F]F(-) with a mixture of K(18)F and Kryptofix (K222) in acetonitrile as standard condition. PET imaging was performed using a dedicated small animal PET scanner.
  
  
  RESULTS
  (18)F-labeled silicon-based misonidazole analogues were easily synthesized in three steps. The hydrolytic and radiolytic stability of these new fluorosilanes depend on the steric hindrance at the silicon center. Indeed, partial uptake of dimethylfluorosilane [(18)F]2a(1-(3-(Fluorodimethylsilyl)propyl)-2-nitro-1H-imidazole) in tumor hypoxic area was observed but defluorination also appeared. Moreover, PET studies indicated that, owing to its high lipophilicity, the most stable dinaphtylfluorosilane [(18)F]2d is retained mainly by the lungs.
  
  
  CONCLUSIONS
  We have described an efficient and versatile approach for the synthesis of (18)F-labeled, silicon-based misonidazole analogues. PET imaging of one of these compounds revealed that hypoxia could be detected. Controlling the biodistribution of (18)F-labeled silicon-based misonidazole analogues will require additional studies.
authors.affiliation: Department of Nuclear Medicine, Henri Becquerel Center and Rouen University Hospital and QuantIF- LITIS (EA4108), Rouen Cedex, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bohn
authors.forename: Abdallah
authors.initials: A
authors.lastname: Deyine
authors.forename: Rabah
authors.initials: R
authors.lastname: Azzouz
authors.forename: Laetitia
authors.initials: L
authors.lastname: Bailly
authors.forename: Catherine
authors.initials: C
authors.lastname: Fiol-Petit
authors.forename: Laurent
authors.initials: L
authors.lastname: Bischoff
authors.forename: Corinne
authors.initials: C
authors.lastname: Fruit
authors.forename: Francis
authors.initials: F
authors.lastname: Marsais
authors.forename: Pierre
authors.initials: P
authors.lastname: Vera
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005354:Fibrosarcoma / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008809:Mice, Inbred C3H; D008920:Misonidazole / Q000737:chemistry* / Q000493:pharmacokinetics*; D009928:Organ Specificity; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D012825:Silicon / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D008920:Misonidazole; D012825:Silicon