Concomitant [18F]F-FAZA and [18F]F-FDG Imaging of Gynecological Cancer Xenografts: Insight into Tumor Hypoxia

Background/Aim: Herein we assessed the feasibility of imaging protocols using both hypoxia-specific [F-18]F-FAZA and [F-18]F-FDG in bypassing the limitations derived from the non-specific findings of [F-18]F-FDG PET imaging of tumor-related hypoxia. Materials and Methods: CoCl2-generated hypoxia was induced in multidrug resistant (Pgp+) or sensitive (Pgp-) human ovarian (Pgp- A2780, Pgp+ A2780AD), and cervix carcinoma (Pgp- KB-3-1, Pgp+ KB-V-1) cell lines to establish corresponding tumor-bearing mouse models. Prior to [F-18]F-FDG/[F-18]F-FAZA-based MiniPET imaging, in vitro [F-18]F-FDG uptake measurements and western blotting were used to verify the presence of hypoxia. Results: Elevated GLUT-1, and hexokinase enzyme-II expression driven by CoCl2-induced activation of hypoxia-inducible factor-1 alpha explains enhanced cellular [F-18]F-FDG accumulation. No difference was observed in the [F-18]F-FAZA accretion of Pgp+ and Pgp- tumors. Tumor-to-muscle ratios for [F-18]F-FAZA measured at 110-120 min postinjection (6.2 +/- 0.1) provided the best contrasted images for the delineation of PET-oxic and PET-hypoxic intratumor regions. Although all tumors exhibited heterogenous uptake of both radiopharmaceuticals, greater differences for [F-18]F-FAZA between the tracer avid and non-accumulating regions indicate its superiority over [F-18]F-FDG. Spatial correlation between [F-18]F-FGD and [F-18]F-FAZA scans confirms that hypoxia mostly occurs in regions with highly active glucose metabolism. Conclusion: The addition of [F-18]F-FAZA PET to [F-18]F-FGD imaging may add clinical value in determining hypoxic sub-regions.