A strategy for improving FDG accumulation for early detection of metastasis from primary pancreatic cancer: stimulation of the Warburg effect in AsPC-1 cells

Nucl Med Biol. 2015 May;42(5):475-481. doi: 10.1016/j.nucmedbio.2014.12.017. Epub 2015 Jan 8.

Abstract

Introduction: Early detection and/or prediction of metastasis provide more prognostic relevance than local recurrence. Direct spread into the peritoneum is frequently found in pancreatic cancer patients, but positron emission tomography (PET) with 2-deoxy-2-fluoro-d-glucose (FDG) is not useful for identifying such metastasis. We investigated a method to enhance FDG accumulation using AsPC-1 human ascites tumor cells.

Methods: (14)C-FDG accumulation was assessed under the following conditions: 1) characteristics of (14)C-FDG transport were examined using phloridzin, a Na(+)-free buffer, and various hexoses, and 2) accumulation of (14)C-FDG was measured in cells that were pretreated with hexose for various time periods, and activity of 6-phosphofructo-1-kinase (PFK-1) was assayed.

Results: (14)C-FDG transport into AsPC-1 cells was mediated primarily by a Na(+)-independent transport mechanism. Aldohexoses such as d-glucose, D-mannose, and D-galactose inhibited (14)C-FDG transport. Cells pretreated with d-glucose, D-mannose, or D-fructose exhibited augmented (14)C-FDG accumulation. Pretreatment with higher concentrations of D-glucose or D-fructose tended to increase PFK-1 activity.

Conclusions: Very little information has been published about the association between PFK-1 and FDG accumulation, and we confirmed the impacts of various hexoses on the activity of PFK-1 and FDG accumulation in AsPC-1 cells. Clarifying the relevance of PFK-1 in FDG accumulation will contribute to developing new features of FDG-PET, because PFK-1 is the main regulator of glycolysis.

Keywords: 6-Phosphofructo-1-kinase; Ascites tumor cells; FDG; Glycolysis; Hexose.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ascites / pathology
  • Biological Transport / drug effects
  • Cell Line, Tumor
  • Early Detection of Cancer / methods*
  • Fluorodeoxyglucose F18 / metabolism*
  • Glycolysis* / drug effects
  • Hexoses / pharmacology
  • Humans
  • Neoplasm Metastasis
  • Pancreatic Neoplasms / pathology*
  • Phosphofructokinase-1 / metabolism
  • Positron-Emission Tomography

Substances

  • Hexoses
  • Fluorodeoxyglucose F18
  • Phosphofructokinase-1