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

We have previously shown that the accumulation of fluorine-18-labeled fluor omisonidazole ([F-18]FMISO) is inversely correlated to tissue oxygenation, allowing the quantification of porcine liver tissue hypoxia in vivo. We det ermined the activity from administered [F-18]FMISO in relation to the hepat ic oxygen availability and the partial pressure of oxygen in tissue (tPO(2) ) to define a critical oxygen delivery on a regional basis, [F-18]FMISO was injected 2 h after onset of regional liver hypoxia due to arterial occlusi on of branches of the hepatic artery in 10 domestic pigs. During the experi mental procedure the fractional concentration of inspired oxygen (FiO(2)) w as set to 0.67 in group A (N = 5) and to 0.21 in group B (N = 5) animals. I mmediately before sacrifice, the tPO(2) was determined in normal flow and f low-impaired liver segments. The standardized uptake values (SUV) for [F-18 ]FMISO was calculated from 659 single tissue samples obtained 3 h after inj ection of approximately 10 MBq/kg body weight [F-18]FMISO and was compared with the regional total hepatic oxygen delivery (DO2) calculated from the r egional arterial and portal venous flow (based on Ce-141- and Tc-99m-micros pheres measurements) and the oxygen content of the arterial and portal veno us blood. In 121 tPO(2)-measured liver tissue samples, the mean DO2 was sig nificantly decreased in occluded liver tissue samples [group A: 0.063 (0.04 4-0.089); group B: 0.036 (0.032-0.066)] compared to normal flow segments [g roup A: 0.117 (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 < 0.00 1 in group B]. The tPO(2) of occluded segments [group A: 5.1 (3.2-8.1); gro up B: 3.9 (2.4-6.2) mm Hg] was significantly decreased compared to normal f low 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 [F-18]FMISO administration, the mean [F-18]FMISO SUV determined in tPO(2)-measured occ luded 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 (1.2-2.0 6), group B: 1.5 (1.16-1.93); P < 0.001 for both groups]. The [F-18]FMISO S UV allowed prediction of the tPO(2) with satisfying accuracy in hypoxic reg ions using the exponential regression curve {[F-18]FMISO = 1.05 + 6.7((-0.1 17 tPO2)); r(2) = 0.75; P < 0.001}, In addition, regardless of ventilation conditions, a significant exponential relationship between the DO2 and the [F-18]FMTSO SUV was found (r(2) = 0.39, P < 0.001). Our results suggest tha t 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 o f hypoxia is reflected by the [F-18]FMISO accumulation and allows the in vi vo estimation of the tPO(2) in hypoxic regions. NUCL MED BIOL 27;8:693-700, 2000. (C) 2000 Elsevier Science Inc. All rights reserved.