Tuomela et al. BMC Cancer 2010, 10:596 http://www.biomedcentral.com/1471-2407/10/596 Page 8 of 14 Figure 4 Perfusion and oxygenation status of tumours. A, Labelling with the perfusion marker Hoechst 33342 showed that the flow in blood vessels was better in the VEGF tumours compared with the FGF8b and mock tumours, where Hoechst 33342 labelling was detected only in the tumour periphery (Bar 200 μm). Examples of the intratumoral distribution of [18F]EF5 in FGF8b, VEGF and mock tumour sections are shown in B. FGF8b and mock tumours showed mainly peripherally located uptake of [18F]EF5, whereas uptake into VEGF tumours was more uniform throughout the tumours. Uptake intensity is not comparable between these images, since they were not corrected for injected dose or cross- calibrated between separate studies. C, The tumour-to-blood (T/B) uptake ratio of [18F]EF5 (T/B ratio) in FGF8b (n = 11), VEGF (n = 12) and mock (n = 29) tumours is expressed as mean ± SD. Accumulation of [18F]EF5 was significantly lower (p < 0.05) in VEGF tumours compared with mock tumours, whereas no significant difference in T/B ratio was seen between FGF8b and mock tumours. Partial pressures of oxygen (pO2) in VEGF (n = 3), FGF8b (n = 3) and mock (n = 3) tumours are shown in D. The mean values of pO2 measurements are shown as a curve. VEGF tumours were relatively well oxygenated in comparison with FGF8b and mock tumours. Discussion Tumour vasculature provides necessary oxygen and nutrients for tumour growth, but it also plays a major role in metastatic spread. In prostate cancer, VEGF- mediated angiogenesis has proved to be important for tumour growth and metastasis [10,50]. VEGF receptors are overexpressed in prostate cancer and plasma levels of VEGF are raised in metastatic disease compared with localised disease or healthy controls. Alterations in the vascular supply influence the tumour microen- vironmental conditions, leading to changes in blood flow, pH, glucose metabolism and oxygenation, which all may have significant effects on the responses of tumours to therapy [5]. Prostate tumours are typically very hypoxic. Hypoxia is known to induce a more aggressive phenotype, which increases metastatic potential, promotes tumour progression and limits the effectiveness of radiation therapy [2,51]. Tumour cells generally show increased glycolysis, even under aerobic conditions, and a rough correlation between the degree of malignancy and glycolytic rate has long been recog- nised [52].