ABSTRACT
PURPOSE: The aims of this study were to evaluate the change of [18F]fluoromisonidazole ([18F]FMISO) uptake in C3H mouse squamous cell carcinoma-VII (SCC-VII) treated with mild hyperthermia (42oC) and nicotinamide and to assess the biodistribution of the markers in normal tissues under similar conditions. METHODS AND MATERIALS: [18F]FMISO was producedby our hospital. Female C3H mice with a C3H SCC-VII tumor grown on their extremities were used. Tumors were size matched. Non-anaesthetized, tumor-bearing mice underwent control or mild hyperthermia at 42oC for 60 min with nicotinamide (50 mg/kg i.p. injected) and were examined by gamma counter, autoradiography and animal PET scan 3 hours after tracer i.v. injected with breathing room air. The biodistribution of these agents were obtained at 3 h after [18F]FMISO injection. Blood, tumor, muscle, heart, lung, liver, kidney, brain, bone, spleen, and intestine were removed, counted for radioactivity and weighed. The tumor and liver were frozen and cut with a cryomicrotome into 10-micrometer sections. The spatial distribution of radioactivity from the tissue sections was determined with digital autoradiography. RESULTS: The mild hyperthermia with nicotinamide treatment had only slight effects on the biodistribution of either marker in normal tissues. We observed that the whole tumor radioactivity uptake ratios were higher in the control mice than in the mild hyperthermia with nicotinamide treated mice for [18F]FMISO (1.56+/-1.03 vs. 0.67+/-0.30; p=0.063). In addition, autoradiography and animal PET scan demonstrated that the area and intensity of [18F]FMISO uptake was significantly decreased. CONCLUSION: Mild hyperthermia and nicotinamide significantly improved tumor hypoxia using [18F]FMISO and this uptake reflected tumor hypoxic status.