Kinetic Evaluation of the Hypoxia Radiotracers [18F]FMISO and [18F]FAZA in Dogs with Spontaneous Tumors Using Dynamic PET/CT Imaging

Abstract

Purpose: We evaluated the kinetics of the hypoxia PET radiotracers, [18F]fluoromisonidazole ([18F]FMISO) and [18F]fluoroazomycin-arabinoside ([18F]FAZA), for tumor hypoxia detection and to assess the correlation of hypoxic kinetic parameters with static imaging measures in canine spontaneous tumors. Methods: Sixteen dogs with spontaneous tumors underwent a 150-min dynamic PET scan using either [18F]FMISO or [18F]FAZA. The maximum tumor-to-muscle ratio (TMRmax) > 1.4 on the last image frame was used as the standard threshold to determine tumor hypoxia. The tumor time-activity curves were analyzed using irreversible and reversible two-tissue compartment models and graphical methods. TMRmax was compared with radiotracer trapping rate (k3), influx rate (Ki), and distribution volume (VT). Results: Tumor hypoxia was detected in 7/8 tumors in the [18F]FMISO group and 4/8 tumors in the [18F]FAZA group. All hypoxic tumors were detected at > 120 min with [18F]FMISO and at > 60 min with [18F]FAZA. [18F]FAZA showed better fit with the reversible model. TMRmax was strongly correlated with the irreversible parameters (k3 and Ki) for [18F]FMISO at > 90 min and with the reversible parameter (VT) for [18F]FAZA at > 120 min. Conclusions: Our results showed that [18F]FAZA provided a promising alternative radiotracer to [18F]FMISO with detecting the presence of tumor hypoxia at an earlier time (60 min), consistent with its favorable faster kinetics. The strong correlation between TMRmax over the 90–150 min and 120–150 min timeframes with [18F]FMISO and [18F]FAZA, respectively, with kinetic parameters associated with tumor hypoxia for each radiotracer, suggests that a static scan measurement (TMRmax) is a good alternative to quantify tumor hypoxia.