title: Dependency of the [18F]fluoromisonidazole uptake on oxygen delivery and tissue oxygenation in the porcine liver.
abstract: We have previously shown that the accumulation of fluorine-18-labeled fluoromisonidazole ([(18)F]FMISO) is inversely correlated to tissue oxygenation, allowing the quantification of porcine liver tissue hypoxia in vivo. We determined the activity from administered [(18)F]FMISO in relation to the hepatic oxygen availability and the partial pressure of oxygen in tissue (tPO(2)) to define a critical oxygen delivery on a regional basis. [(18)F]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 (FiO(2)) was set to 0.67 in group A ( N=5) and to 0.21 in group B ( N=5) animals. Immediately before sacrifice, the tPO(2) was determined in normal flow and flow-impaired liver segments. The standardized uptake values (SUV) for [(18)F]FMISO was calculated from 659 single tissue samples obtained 3 h after injection of approximately 10 MBq/kg body weight [(18)F]FMISO and was compared with the regional total hepatic oxygen delivery (DO(2)) calculated from the regional arterial and portal venous flow (based on (141)Ce- and (99m)Tc-microspheres measurements) and the oxygen content of the arterial and portal venous blood. In 121 tPO(2)-measured liver tissue samples, the mean DO(2) 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 x min(-1) x g(-1); geometric mean (95% confidence limits); p < 0.01 in group A and p < 0.001 in group B]. The tPO(2) 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 [(18)F]FMISO administration, the mean [(18)F]FMISO SUV determined in tPO(2)-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 [(18)F]FMISO SUV allowed prediction of the tPO(2) with satisfying accuracy in hypoxic regions using the exponential regression curve [[(18)F]FMISO=1.05+6.7((-0.117 tPO(2))); r(2)=0.75; p < 0.001]. In addition, regardless of ventilation conditions, a significant exponential relationship between the DO(2) and the [(18)F]FMISO SUV was found ( r(2)=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 x min(-1) x g(-1) regularly causes liver tissue hypoxia. The severity of hypoxia is reflected by the [(18)F]FMISO accumulation and allows the in vivo estimation of the tPO(2) in hypoxic regions.
authors.affiliation: Department of General Surgery, University of Tübingen, Tübingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Piert
authors.forename: H J
authors.initials: HJ
authors.lastname: Machulla
authors.forename: G
authors.initials: G
authors.lastname: Becker
authors.forename: P
authors.initials: P
authors.lastname: Aldinger
authors.forename: E
authors.initials: E
authors.lastname: Winter
authors.forename: R
authors.initials: R
authors.lastname: Bares
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D004566:Electrodes; D005260:Female; D005462:Fluorine Radioisotopes; D006439:Hemodynamics; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism*; D008863:Microspheres; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D013552:Swine; D014055:Tomography, Emission-Computed
chemical_list: D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; C031843:fluoromisonidazole; D008920:Misonidazole; D010100:Oxygen