Positron emission tomography probe demonstrates a striking concentration of ribose salvage in the liver

Proc Natl Acad Sci U S A. 2014 Jul 15;111(28):E2866-74. doi: 10.1073/pnas.1410326111. Epub 2014 Jun 30.

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.

Keywords: Slc2a2; molecular imaging; sugar metabolism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arabinose / analogs & derivatives
  • Arabinose / pharmacology
  • Cell Line
  • Disease Models, Animal
  • Fluorine Radioisotopes / pharmacology
  • Glucose / genetics
  • Glucose / metabolism
  • Glucose Transporter Type 2 / metabolism
  • Humans
  • Lipid Metabolism
  • Liver* / diagnostic imaging
  • Liver* / metabolism
  • Metabolic Syndrome / diagnostic imaging
  • Metabolic Syndrome / metabolism
  • Mice
  • Organ Specificity
  • Positron-Emission Tomography / methods*
  • Radiography
  • Radiopharmaceuticals / pharmacology*
  • Ribose / metabolism*

Substances

  • 2'-deoxy-2'-fluoroarabinose
  • Fluorine Radioisotopes
  • Glucose Transporter Type 2
  • Radiopharmaceuticals
  • Slc2a2 protein, mouse
  • Ribose
  • Arabinose
  • Glucose