Hypoxia is an important resistance factor in
radiotherapy and measuring its spatial distribution in
tumors non-invasively is therefore of major importance. This study characterizes the hypoxic conditions of three
tumor sublines (AT1, HI and H) of the Dunning R3327 prostate
tumor model, which differ in histology, differentiation degree, volume doubling time and androgenic sensitivity, using dynamic
Fluoromisonidazole ((18)F-FMISO)-Positron Emission Tomography/Computed Tomography (PET-CT) and histology. Measurements were performed for two
tumor volumes (average 0.8±0.5 cm(3) vs 4.4±2.8 cm(3)). Data were analyzed according to
tumor subline as well as to the shape of the time activity curves (TACs), based on standardized uptake values (SUVs) and a two-tissue compartment model. Quantitative immunohistochemical studies of the hypoxic fraction, vessel density and vessel size were performed using
pimonidazole,
Hoechst 33342 and CD31
dyes. No significant
FMISO uptake was found in small
tumors, which had a mean SUV of 0.64±0.36, 0.55±0.10 and 0.45±0.08, for AT1, HI and H sublines respectively. In large
tumors, the SUVs were 1.33±0.52, 1.12±0.83 and 0.63±0.16 for AT1, HI and H sublines and the corresponding hypoxic fractions obtained with
pimonidazole staining were 0.62±0.23, 0.54±0.24 and 0.07±0.10, respectively. The AT1- was the most and H-
tumor was the least hypoxic for both methods (P<0.05). All measurements were able to discriminate different hypoxic conditions, however despite SUV and kinetic parameters correlated with the three identified TAC shapes, most of the histological results did not. These results demonstrate impact and limitations of static and dynamic PET-CT measurements to assess
hypoxia non-invasively.