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

Abstract

IntroductionEarly 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. Methods14C-FDG accumulation was assessed under the following conditions: 1) characteristics of 14C-FDG transport were examined using phloridzin, a Na+-free buffer, and various hexoses, and 2) accumulation of 14C-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. Results14C-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 14C-FDG transport. Cells pretreated with d-glucose, d-mannose, or d-fructose exhibited augmented 14C-FDG accumulation. Pretreatment with higher concentrations of d-glucose or d-fructose tended to increase PFK-1 activity. ConclusionsVery 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.