Nucl Med Mol Imaging.  2023 Feb;57(1):16-25. s13139-022-00780-4.

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

Affiliations
  • 1Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA
  • 2Department of Radiology, School of Medicine, University of California, CA, Sacramento, USA
  • 3Department of Biomedical Engineering, College of Engineering, University of California, Davis, CA, USA
  • 4Omniox Inc, Palo Alto, CA, USA

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 ­(TMR max ) > 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. T­MR max was compared with radiotracer trapping rate (k 3 ), influx rate (K i ), and distribution volume (V T ).
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. ­TMR max was strongly correlated with the irreversible parameters (k3 and Ki ) for [18F]FMISO at > 90 min and with the reversible parameter (V T ) 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 betwee TMR max 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 ( ­TMR max ) is a good alternative to quantify tumor hypoxia.

Keyword

Nuclear scintigraphy; Hypoxia; Companion animal; Neoplasia; Kinetic modeling
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