title: Evaluation of hypoxia in an experimental rat tumour model by [(18)F]fluoromisonidazole PET and immunohistochemistry.
abstract: 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.
authors.affiliation: Department of Nuclear Medicine, University Hospital Gasthuisberg and KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Dubois
authors.forename: W
authors.initials: W
authors.lastname: Landuyt
authors.forename: K
authors.initials: K
authors.lastname: Haustermans
authors.forename: P
authors.initials: P
authors.lastname: Dupont
authors.forename: G
authors.initials: G
authors.lastname: Bormans
authors.forename: P
authors.initials: P
authors.lastname: Vermaelen
authors.forename: P
authors.initials: P
authors.lastname: Flamen
authors.forename: E
authors.initials: E
authors.lastname: Verbeken
authors.forename: L
authors.initials: L
authors.lastname: Mortelmans
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D024403:Carbonic Anhydrase III / Q000276:immunology / Q000378:metabolism; D015687:Cell Hypoxia; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006321:Heart / Q000502:physiology; D007124:Immunoenzyme Techniques; D008168:Lung / Q000378:metabolism; D008297:Male; D008920:Misonidazole / Q000031:analogs & derivatives*; D009132:Muscles / Q000378:metabolism; D009593:Nitroimidazoles / Q000276:immunology / Q000378:metabolism; D049268:Positron-Emission Tomography; D011838:Radiation-Sensitizing Agents; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D012208:Rhabdomyosarcoma / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D019275:Radiopharmaceuticals; C031843:fluoromisonidazole; D019788:Fluorodeoxyglucose F18; C033815:pimonidazole; D008920:Misonidazole; D024403:Carbonic Anhydrase III