title: Positron emission tomography probe demonstrates a striking concentration of ribose salvage in the liver.
abstract: PET is a powerful technique for quantifying and visualizing biochemical pathways in vivo. Here, we develop and validate a novel PET probe, [(18)F]-2-deoxy-2-fluoroarabinose ([(18)F]DFA), for in vivo imaging of ribose salvage. DFA mimics ribose in vivo and accumulates in cells following phosphorylation by ribokinase and further metabolism by transketolase. We use [(18)F]DFA to show that ribose preferentially accumulates in the liver, suggesting a striking tissue specificity for ribose metabolism. We demonstrate that solute carrier family 2, member 2 (also known as GLUT2), a glucose transporter expressed in the liver, is one ribose transporter, but we do not know if others exist. [(18)F]DFA accumulation is attenuated in several mouse models of metabolic syndrome, suggesting an association between ribose salvage and glucose and lipid metabolism. These results describe a tool for studying ribose salvage and suggest that plasma ribose is preferentially metabolized in the liver.
authors: Departments of Microbiology, Immunology, and Molecular Genetics, pclark@mednet.ucla.edu mphelps@mednet.ucla.edu owenwitte@mednet.ucla.edu.
authors: Peter M
authors: PM
authors: Clark
authors: Molecular and Medical Pharmacology,Crump Institute for Molecular Imaging.
authors: Graciela
authors: G
authors: Flores
authors: Molecular and Medical Pharmacology,Chemistry and Biochemistry, and.
authors: Nikolai M
authors: NM
authors: Evdokimov
authors: Molecular and Medical Pharmacology.
authors: Melissa N
authors: MN
authors: McCracken
authors: Departments of Microbiology, Immunology, and Molecular Genetics.
authors: Timothy
authors: T
authors: Chai
authors: Molecular and Medical Pharmacology.
authors: Evan
authors: E
authors: Nair-Gill
authors: Division of Digestive Diseases.
authors: Fiona
authors: F
authors: O'Mahony
authors: Division of Digestive Diseases.
authors: Simon W
authors: SW
authors: Beaven
authors: Pasarow Mass Spectrometry Laboratory, Semel Institute for Neuroscience and Human Behavior,Psychiatry and Biobehavioral Sciences.
authors: Kym F
authors: KF
authors: Faull
authors: Molecular and Medical Pharmacology,Crump Institute for Molecular Imaging, pclark@mednet.ucla.edu mphelps@mednet.ucla.edu owenwitte@mednet.ucla.edu.
authors: Michael E
authors: ME
authors: Phelps
authors: Chemistry and Biochemistry, and.
authors: Michael E
authors: ME
authors: Jung
authors: Departments of Microbiology, Immunology, and Molecular Genetics,Molecular and Medical Pharmacology,Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, andHoward Hughes Medical Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095 pclark@mednet.ucla.edu mphelps@mednet.ucla.edu owenwitte@mednet.ucla.edu.
authors: Owen N
authors: ON
authors: Witte
mesh_terms: D000818:Animals; D001089:Arabinose / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D004195:Disease Models, Animal; D005462:Fluorine Radioisotopes / Q000494:pharmacology; D005947:Glucose / Q000235:genetics / Q000378:metabolism; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D024821:Metabolic Syndrome / Q000000981:diagnostic imaging / Q000378:metabolism; D051379:Mice; D009928:Organ Specificity; D049268:Positron-Emission Tomography / Q000379:methods*; D011859:Radiography; D019275:Radiopharmaceuticals / Q000494:pharmacology*; D012266:Ribose / Q000378:metabolism*
chemical_list: C118537:2'-deoxy-2'-fluoroarabinose; D005462:Fluorine Radioisotopes; D051273:Glucose Transporter Type 2; D019275:Radiopharmaceuticals; C495682:Slc2a2 protein, mouse; D012266:Ribose; D001089:Arabinose; D005947:Glucose
keywords: Slc2a2; molecular imaging; sugar metabolism