Evaluation of hypoxia in an experimental rat tumour model by [(18)F]fluoromisonidazole PET and immunohistochemistry

Br J Cancer. 2004 Nov 29;91(11):1947-54. doi: 10.1038/sj.bjc.6602219.


This study aimed to evaluate tumour hypoxia by comparing [(18)F]Fluoromisonidazole uptake measured using positron emission tomography ([(18)F]FMISO-PET) with immunohistochemical (IHC) staining techniques. Syngeneic rhabdomyosarcoma (R1) tumour pieces were transplanted subcutaneously in the flanks of WAG/Rij rats. Tumours were analysed at volumes between 0.9 and 7.3 cm(3). Hypoxic volumes were defined using a 3D region of interest on 2 h postinjection [(18)F]FMISO-PET images, applying different thresholds (1.2-3.0). Monoclonal antibodies to pimonidazole (PIMO) and carbonic anhydrase IX (CA IX), exogenous and endogenous markers of hypoxia, respectively, were used for IHC staining. Marker-positive fractions were microscopically measured for each tumour, and hypoxic volumes were calculated. A heterogeneous distribution of hypoxia was observed both with histology and [(18)F]FMISO autoradiography. A statistically significant correlation (P<0.05) was obtained between the hypoxic volumes defined with [(18)F]FMISO-PET and the volumes derived from the PIMO-stained tumour sections (r=0.9066; P=0.0001), regardless of the selected threshold between 1.4 and 2.2. A similar observation was made with the CA IX staining (r=0.8636; P=0.0006). The relationship found between [(18)F]FMISO-PET and PIMO- and additionally CA IX-derived hypoxic volumes in rat rhabdomyosarcomas indicates the value of the noninvasive imaging method to measure hypoxia in whole tumours.

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Carbonic Anhydrase III / immunology
  • Carbonic Anhydrase III / metabolism
  • Cell Hypoxia*
  • Fluorodeoxyglucose F18* / pharmacokinetics
  • Heart / physiology
  • Immunoenzyme Techniques
  • Lung / metabolism
  • Male
  • Misonidazole / analogs & derivatives*
  • Muscles / metabolism
  • Nitroimidazoles / immunology
  • Nitroimidazoles / metabolism
  • Positron-Emission Tomography*
  • Radiation-Sensitizing Agents
  • Radiopharmaceuticals / pharmacokinetics
  • Rats
  • Rhabdomyosarcoma / diagnostic imaging*
  • Rhabdomyosarcoma / metabolism
  • Rhabdomyosarcoma / pathology


  • Antibodies, Monoclonal
  • Nitroimidazoles
  • Radiation-Sensitizing Agents
  • Radiopharmaceuticals
  • fluoromisonidazole
  • Fluorodeoxyglucose F18
  • pimonidazole
  • Misonidazole
  • Carbonic Anhydrase III