Assessment of intratumor hypoxia by integrated 18F-FDG PET / perfusion CT in a liver tumor model

PLoS One. 2017 Mar 6;12(3):e0173016. doi: 10.1371/journal.pone.0173016. eCollection 2017.

Abstract

Objectives: Hypoxia in solid tumors occurs when metabolic demands in tumor cells surpass the delivery of oxygenated blood. We hypothesize that the 18F-fluorodeoxyglucose (18F-FDG) metabolism and tumor blood flow mismatch would correlate with tumor hypoxia.

Methods: Liver perfusion computed tomography (CT) and 18F-FDG positron emission tomography (PET) imaging were performed in twelve rabbit livers implanted with VX2 carcinoma. Under CT guidance, a fiber optic probe was inserted into the tumor to measure the partial pressure of oxygen (pO2). Tumor blood flow (BF) and standardized uptake value (SUV) were measured to calculate flow-metabolism ratio (FMR). Tumor hypoxia was further identified using pimonidazole immunohistochemical staining. Pearson correlation analysis was performed to determine the correlation between the imaging parameters and pO2 and pimonidazole staining.

Results: Weak correlations were found between blood volume (BV) and pO2 level (r = 0.425, P = 0.004), SUV and pO2 (r = -0.394, P = 0.007), FMR and pimonidazole staining score (r = -0.388, P = 0.031). However, there was stronger correlation between tumor FMR and pO2 level (r = 0.557, P < 0.001).

Conclusions: FMR correlated with tumor oxygenation and pimonidazole staining suggesting it may be a potential hypoxic imaging marker in liver tumor.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Fluorodeoxyglucose F18*
  • Glucose / metabolism
  • Humans
  • Hypoxia / metabolism*
  • Liver Neoplasms / diagnostic imaging*
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Male
  • Neovascularization, Pathologic / diagnostic imaging
  • Neovascularization, Pathologic / metabolism
  • Nitroimidazoles / administration & dosage
  • Nitroimidazoles / metabolism
  • Oxygen Consumption
  • Perfusion
  • Positron Emission Tomography Computed Tomography*
  • Positron-Emission Tomography
  • Rabbits

Substances

  • Nitroimidazoles
  • Fluorodeoxyglucose F18
  • pimonidazole
  • Glucose

Grants and funding

TYL was funded by Ontario Institute of Cancer Research (Wester REB #103184) http://oicr.on.ca/.