Dependency of the [18F]fluoromisonidazole uptake on oxygen delivery and tissue oxygenation in the porcine liver

We have previously shown that the accumulation of fluorine-18-labeled fluoromisonidazole (¹⁸F]FMISO) is inversely correlated to tissue oxygenation, allowing the quantification of porcine liver tissue hypoxia in vivo. We determined the activity from administered ¹⁸F]FMISO in relation to the hepatic oxygen availability and the partial pressure of oxygen in tissue (tPO₂) to define a critical oxygen delivery on a regional basis. ¹⁸F]FMISO was injected 2 h after onset of regional liver hypoxia due to arterial occlusion of branches of the hepatic artery in 10 domestic pigs. During the experimental procedure the fractional concentration of inspired oxygen (FiO₂) was set to 0.67 in group A ( N=5) and to 0.21 in group B ( N=5) animals. Immediately before sacrifice, the tPO₂ was determined in normal flow and flow-impaired liver segments. The standardized uptake values (SUV) for ¹⁸F]FMISO was calculated from 659 single tissue samples obtained 3 h after injection of approximately 10 MBq/kg body weight ¹⁸F]FMISO and was compared with the regional total hepatic oxygen delivery (DO₂) calculated from the regional arterial and portal venous flow (based on ¹⁴¹Ce- and ^99mTc-microspheres measurements) and the oxygen content of the arterial and portal venous blood. In 121 tPO₂-measured liver tissue samples, the mean DO₂ was significantly decreased in occluded liver tissue samples group A: 0.063 (0.044–0.089); group B: 0.046 (0.032–0.066)] compared to normal flow segments group A: 0.177 (0.124–0.252); group B: 0.179 (0.128–0.25) mL·min^?1·g^?1; geometric mean (95% confidence limits); p < 0.01 in group A and p < 0.001 in group B]. The tPO₂ of occluded segments group A: 5.1 (3.2–8.1); group B: 3.9 (2.4–6.2) mm Hg] was significantly decreased compared to normal flow segments group A: 20.2 (12.6–32.5); group B: 22.4 (14.3–35.2) mm Hg; p < 0.01 in group A and p < 0.001 in group B]. Three hours after ¹⁸F]FMISO administration, the mean ¹⁸F]FMISO SUV determined in tPO₂-measured occluded segments was significantly higher group A: 4.08 (3.12–5.34), group B: 5.43 (4.14–7.13)] compared to normal liver tissue group A: 1.57 (1.2–2.06), group B: 1.5 (1.16–1.93); p < 0.001 for both groups]. The ¹⁸F]FMISO SUV allowed prediction of the tPO₂ with satisfying accuracy in hypoxic regions using the exponential regression curve { ¹⁸F]FMISO=1.05+6.7^{(?0.117 tPO₂}); r²=0.75;p < 0.001}. In addition, regardless of ventilation conditions, a significant exponential relationship between the DO₂ and the ¹⁸F]FMISO SUV was found ( r²=0.39,p < 0.001). Our results suggest that the reduction of the oxygen delivery below the critical range of 0.1–0.11 mL·min^?1·g^?1 regularly causes liver tissue hypoxia. The severity of hypoxia is reflected by the ¹⁸F]FMISO accumulation and allows the in vivo estimation of the tPO₂ in hypoxic regions.