Introducing fluorine-18 fluoromisonidazole positron emission tomography for the localisation and quantification of pig liver hypoxia

Fluorine-18 labelled fluoromisonidazole ([F-18]FMISO) has been shown to accumulate in hypoxic tissue in inverse proportion to tissue oxygenation. In order to evaluate the potential of [F-18]FMISO as a possible positron emission tomography (PET) tracer for imaging of liver tissue hypoxia, we measured the [F-18]FMISO uptake in 13 domestic pigs using dynamic PET scanning. Hypoxia was induced by segmental arterial hepatic occlusion. During the experimental procedure the fractional concentration of inspired oxygen (FiO(2)) was set to 0.67 in group A (n=6) and to 0.21 in group B (n=7) animals. Before and after arterial occlusion, the partial pressure of O-2 in tissue (TPO2) and the arterial blood flow were determined in normal flow and flow-impaired liver segments. Standardised uptake values [SUV=kBq tissue tin g) / body weight tin kg) x injected dose tin kBq)] for [F-18]FMISO were calculated from PET images obtained 3 hours after injection of about 10 MBq/kg body weight [F-18]FMISO. Immediately before PET scanning, the mean arterial blood flow was significantly decreased in arterially occluded segments [group A: 0.41 (0.32-0.52); group B: 0.24 (0.16-0.33) mi; min(-1) g(-1)] compared with normal flow segments [group A: 1.05 (0.76-1.46); group B: 1.14 (0.83-1.57) ml min(-1) g(-1); geometric mean (95% confidence limits); P<0.001 for both groups]. After PET scanning, the TPO2 of occluded segments (group A: 5.1 (4.1-6.4); group B: 3.5 (2.6-4.9) mmHg] was significantly decreased compared with normal flow segments [group A: 26.4 (21.2-33.0); group B: 18.2 (13.3-25.1) mmHg; P<0.001 for both groups]. During the 3-h PET scan, the mean [F-18]FMISO SUV determined in occluded segments increased significantly to 3.84 (3.12-4.72) in group A and 5.7 (4.71-6.9) in group B, while the SUV remained unchanged in corresponding normal liver tissue [group A: 1.4 (1.14-1.71); group B: 1.31 (1.09-1.57); P<0.001 for both groups]. Regardless of ventilation conditions, a significant inverse exponential relationship was found between the TPO2 and the [F-18]FMISO SUV (r(2)=0.88, P<0.001). Our results suggest that because tracer delivery to hypoxic tissues was maintained by the portal circulation, the [F-18]FMISO accumulation in the liver was found to be directly related to the severity of tissue hypoxia. Thus, [F-18]FMISO PET allows in vivo quantification of pig liver hypoxia using simple SUV analysis as long as tracer delivery is not critically reduced.