title: f-[18F]fluoroethanol and 3-[18F]fluoropropanol: facile preparation, biodistribution in mice, and their application as nucleophiles in the synthesis of [18F]fluoroalkyl aryl ester and ether PET tracers.
abstract: BACKGROUND
  2-[(18)F]Fluoroethoxy and 3-[(18)F]fluoropropoxy groups are common moieties in the structures of radiotracers used with positron emission tomography. The objectives of this study were (1) to develop an efficient one-step method for the preparation of 2-[(18)F]fluoroethanol (2-[(18)F]FEtOH) and 3-[(18)F]fluoropropanol (3-[(18)F]FPrOH); (2) to demonstrate the feasibility of using 2-[(18)F]FEtOH as a nucleophile for the synthesis of 2-[(18)F]fluoroethyl aryl esters and ethers; and (3) to determine the biodistribution profiles of 2-[(18)F]FEtOH and 3-[(18)F]FPrOH in mice.
  
  
  METHODS
  2-[(18)F]FEtOH and 3-[(18)F]FPrOH were prepared by reacting n-Bu4N[(18)F]F with ethylene carbonate and 1,3-dioxan-2-one, respectively, in diethylene glycol at 165°C and purified by distillation. 2-[(18)F]fluoroethyl 4-fluorobenzoate and 1-(2-[(18)F]fluoroethoxy)-4-nitrobenzene were prepared by coupling 2-[(18)F]FEtOH with 4-fluorobenzoyl chloride and 1-fluoro-4-nitrobenzene, respectively. Biodistribution and PET/CT imaging studies of 2-[(18)F]FEtOH and 3-[(18)F]FPrOH were performed in normal female Balb/C mice.
  
  
  RESULTS
  The preparation of 2-[(18)F]FEtOH and 3-[(18)F]FPrOH took 60 min, and their decay-corrected yields were 88.6 ± 2.0% (n = 9) and 65.6 ± 10.2% (n = 5), respectively. The decay-corrected yields for the preparation of 2-[(18)F]fluoroethyl 4-fluorobenzoate and 1-(2-[(18)F]fluoroethoxy)-4-nitrobenzene were 36.1 ± 5.4% (n = 3) and 27.7 ± 10.7% (n = 3), respectively. Imaging/biodistribution studies in mice using 2-[(18)F]FEtOH showed high initial radioactivity accumulation in all major organs followed by very slow clearance. On the contrary, by using 3-[(18)F]FPrOH, radioactivity accumulated in all major organs was cleared rapidly, but massive in vivo defluorination (31.3 ± 9.57%ID/g in bone at 1h post-injection) was observed.
  
  
  CONCLUSIONS
  Using 2-[(18)F]FEtOH/3-[(18)F]FPrOH as a nucleophile is a competitive new strategy for the synthesis of 2-[(18)F]fluoroethyl/3-[(18)F]fluoropropyl aryl esters and ethers. Our biodistribution data emphasize the importance of in vivo stability of PET tracers containing a 2-[(18)F]fluoroethyl or 3-[(18)F]fluoropropyl group due to high background and high bone uptake resulting from 2-[(18)F]FEtOH and 3-[(18)F]FPrOH, respectively. This is especially important for their aryl ester derivatives which are prone to in vivo hydrolysis.
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, BC, Canada V5Z1L3.
authors.forename: Jinhe
authors.initials: J
authors.lastname: Pan
authors.forename: Maral
authors.initials: M
authors.lastname: Pourghiasian
authors.forename: Navjit
authors.initials: N
authors.lastname: Hundal
authors.forename: Joseph
authors.initials: J
authors.lastname: Lau
authors.forename: François
authors.initials: F
authors.lastname: Bénard
authors.forename: Shoukat
authors.initials: S
authors.lastname: Dedhar
authors.forename: Kuo-Shyan
authors.initials: KS
authors.lastname: Lin
mesh_terms: D000818:Animals; D004952:Esters; D000431:Ethanol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D004987:Ethers / Q000737:chemistry*; D005240:Feasibility Studies; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D049268:Positron-Emission Tomography / Q000379:methods*; D020005:Propanols / Q000493:pharmacokinetics*; D011849:Radioactive Tracers; D011854:Radiochemistry / Q000379:methods*; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed
chemical_list: D004952:Esters; D004987:Ethers; D020005:Propanols; D011849:Radioactive Tracers; D000431:Ethanol; C001236:2-fluoroethanol
keywords: 3-[(18)F]fluoropropanol; Fluorine-18, 2-[(18)F]fluoroethanol; In vivo defluorination; Positron emission tomography