Pharmacokinetic analysis of [18F]FAZA in non-small cell lung cancer patients

[F-18]Fluoroazomycin arabinoside (FAZA) is a positron emission tomography (PET) tracer developed to enable identification of hypoxic regions within a tumour. The aims of this study were to determine the optimal kinetic model along with validation of using alternatives to arterial blood sampling for analysing [F-18]FAZA studies and to assess the validity of simplified analytical methods. Dynamic 70-min [F-18]FAZA PET/CT scans were obtained from nine non-small cell lung cancer patients. Continuous arterial blood sampling, together with manual arterial and venous sampling, was performed to derive metabolite-corrected plasma input functions. Volumes of interest (VOIs) were defined for tumour, healthy lung muscle and adipose tissue generating [F-18]FAZA time-activity curves (TACs). TACs were analysed using one- and two-tissue compartment models using both metabolite-corrected blood sampler plasma input functions (BSIF) and image-derived plasma input functions (IDIF). The reversible two-tissue compartment model with blood volume parameter (2T4k+V-B) best described kinetics of [F-18]FAZA in tumours. Volumes of distribution (V-T) obtained using IDIF correlated well with those derived using BSIF (R-2=0.82). Venous samples yielded the same radioactivity concentrations as arterial samples for times > 50 min post-injection (p.i.). In addition, both plasma to whole blood ratios and parent fractions were essentially the same for venous and arterial samples. Both standardised uptake value (SUV), normalised to lean body mass, and tumour to blood ratio correlated well with V-T (R-2=0.77 and R-2=0.87, respectively, at 50-60 min p.i.), although a bias was observed at low V-T. The 2T4k+V-B model provided the best fit to the dynamic [F-18]FAZA data. IDIF with venous blood samples can be used as input function. Further data are needed to validate the use of simplified methods.