Glucose metabolism gene expression patterns and tumor uptake of ¹⁸F-fluorodeoxyglucose after radiation treatment

Int J Radiat Oncol Biol Phys. 2014 Nov 1;90(3):620-7. doi: 10.1016/j.ijrobp.2014.06.062. Epub 2014 Sep 26.

Abstract

Purpose: To investigate whether radiation treatment influences the expression of glucose metabolism genes and compromises the potential use of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) as a tool to monitor the early response of head and neck cancer xenografts to radiation therapy (RT).

Methods and materials: Low passage head and neck squamous cancer cells (UT14) were injected to the flanks of female nu/nu mice to generate xenografts. After tumors reached a size of 500 mm(3) they were treated with either sham RT or 15 Gy in 1 fraction. At different time points, days 3, 9, and 16 for controls and days 4, 7, 12, 21, 30, and 40 after irradiation, 2 to 3 mice were assessed with dynamic FDG-PET acquisition over 2 hours. Immediately after the FDG-PET the tumors were harvested for global gene expression analysis and immunohistochemical evaluation of GLUT1 and HK2. Different analytic parameters were used to process the dynamic PET data.

Results: Radiation had no effect on key genes involved in FDG uptake and metabolism but did alter other genes in the HIF1α and glucose transport-related pathways. In contrast to the lack of effect on gene expression, changes in the protein expression patterns of the key genes GLUT1/SLC2A1 and HK2 were observed after radiation treatment. The changes in GLUT1 protein expression showed some correlation with dynamic FDG-PET parameters, such as the kinetic index.

Conclusion: (18)F-fluorodeoxyglucose positron emission tomography changes after RT would seem to represent an altered metabolic state and not a direct effect on the key genes regulating FDG uptake and metabolism.

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / radiotherapy
  • Cell Line, Tumor
  • Female
  • Fluorodeoxyglucose F18 / pharmacokinetics*
  • Gene Expression / radiation effects*
  • Glucose / metabolism*
  • Glucose Transporter Type 1 / genetics
  • Glucose Transporter Type 1 / metabolism*
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / radiotherapy
  • Heterografts
  • Hexokinase / genetics
  • Hexokinase / metabolism*
  • Immunohistochemistry
  • Mice, Nude
  • Positron-Emission Tomography / methods*
  • RNA, Messenger / metabolism
  • Radiopharmaceuticals / pharmacokinetics*
  • Random Allocation
  • Tumor Burden

Substances

  • Glucose Transporter Type 1
  • RNA, Messenger
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • Hexokinase
  • Glucose