title: Efficient synthesis of a fluorine-18 labeled biotin derivative.
abstract: BACKGROUND
  The natural occurring vitamin biotin, also known as vitamin H or vitamin B(7), plays a major role in various metabolic reactions. Caused by its high binding affinity to the protein avidin with a dissociation constant of about 10(-15)M the biotin-avidin system was extensively examined for multiple applications. We have synthesized a fluorine-18 labeled biotin derivative [(18)F]4 for a potential application in positron emission tomography (PET).
  
  
  METHODS
  Mesylate precursor 3 was obtained by an efficient two-step reaction via a copper catalyzed azide-alkyne cycloaddition (CuAAC) from easily accessible starting materials. [(18)F]4 was successfully synthesized by a nucleophilic radiofluorination of precursor 3. A biodistribution study by means of small-animal PET imaging in wt-mice was performed and serum stability was examined.
  
  
  RESULTS
  Compound [(18)F]4 was obtained from precursor compound 3 with an average specific activity of 16GBq/μmol within 45min and a radiochemical yield of 45±5% (decay corrected). [(18)F]4 demonstrated only negligible decomposition in human serum. A qualitative binding study revealed the high affinity of the synthesized biotin derivative to avidin. Blocking experiments with native biotin showed that binding was site-specific. Biodistribution studies showed that [(18)F]4 was cleared quickly and efficiently from the body by hepatobiliary and renal elimination.
  
  
  CONCLUSIONS
  An efficient synthesis for [(18)F]4 was established. In vivo characteristics were determined and demonstrated the pharmacokinetic behaviour of [(18)F]4.
authors.affiliation: University Hospital Münster, Department of Nuclear Medicine, Albert-Schweitzer-Campus 1, Building A1, 48149 Münster, Germany. claesene@uni-muenster.de
authors.forename: Michael
authors.initials: M
authors.lastname: Claesener
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Breyholz
authors.forename: Sven
authors.initials: S
authors.lastname: Hermann
authors.forename: Andreas
authors.initials: A
authors.lastname: Faust
authors.forename: Stefan
authors.initials: S
authors.lastname: Wagner
authors.forename: Otmar
authors.initials: O
authors.lastname: Schober
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfers
authors.forename: Klaus
authors.initials: K
authors.lastname: Kopka
mesh_terms: D000818:Animals; D001710:Biotin / Q000097:blood / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D060326:Chemistry Techniques, Synthetic; D004355:Drug Stability; D005462:Fluorine Radioisotopes; D006801:Humans; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D049268:Positron-Emission Tomography
chemical_list: D005462:Fluorine Radioisotopes; D001710:Biotin