title: Development of 2-Deoxy-2-[(18)F]fluororibose for Positron Emission Tomography Imaging Liver Function in Vivo.
abstract: Life-threatening acute liver failure can be triggered by a variety of factors, including common drugs such as acetaminophen. Positron emission tomography (PET) is rarely used to monitor liver function, in part because of a lack of specific imaging agents for liver function. Here we report a new PET probe, 2-deoxy-2-[(18)F]fluororibose ([(18)F]-2-DFR), for use in imaging liver function. [(18)F]-2-DFR was synthesized and validated as a competitive substrate for the ribose salvage pathway. [(18)F]-2-DFR was prepared through an efficient late stage radiofluorination. The desired selectivity of fluorination was achieved using an unorthodox protecting group on the precursor, which could withstand harsh SN2 reaction conditions with no side reactions. [(18)F]-2-DFR accumulated preferentially in the liver and was metabolized by the same enzymes as ribose. [(18)F]-2-DFR could distinguish between healthy liver and liver damaged by acetaminophen. [(18)F]-2-DFR is expected to be a useful PET probe for imaging and quantifying liver functions in vivo, with likely significant clinical utility.
authors.affiliation: †Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, United States.
authors.forename: Nikolai M
authors.initials: NM
authors.lastname: Evdokimov
authors.forename: Peter M
authors.initials: PM
authors.lastname: Clark
authors.forename: Graciela
authors.initials: G
authors.lastname: Flores
authors.forename: Timothy
authors.initials: T
authors.lastname: Chai
authors.forename: Kym F
authors.initials: KF
authors.lastname: Faull
authors.forename: Michael E
authors.initials: ME
authors.lastname: Phelps
authors.forename: Owen N
authors.initials: ON
authors.lastname: Witte
authors.affiliation: †Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, United States.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Jung
mesh_terms: D000818:Animals; D002460:Cell Line; D003855:Deoxyribose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D055808:Drug Discovery; D005260:Female; D005462:Fluorine Radioisotopes; D054879:Halogenation; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging* / Q000502:physiology*; D008297:Male; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D003855:Deoxyribose; C033285:2'-deoxy-2'-fluororibose