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

Abstract

Background/aim: Herein we assessed the feasibility of imaging protocols using both hypoxia-specific [¹⁸F]F-FAZA and [¹⁸F]F-FDG in bypassing the limitations derived from the non-specific findings of [¹⁸F]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 [¹⁸F]F-FDG/[¹⁸F]F-FAZA-based MiniPET imaging, in vitro [¹⁸F]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-1α explains enhanced cellular [¹⁸F]F-FDG accumulation. No difference was observed in the [¹⁸F]F-FAZA accretion of Pgp+ and Pgp- tumors. Tumor-to-muscle ratios for [¹⁸F]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 [¹⁸F]F-FAZA between the tracer avid and non-accumulating regions indicate its superiority over [¹⁸F]F-FDG. Spatial correlation between [¹⁸F]F-FGD and [¹⁸F]F-FAZA scans confirms that hypoxia mostly occurs in regions with highly active glucose metabolism.

Conclusion: The addition of [¹⁸F]F-FAZA PET to [¹⁸F]F-FGD imaging may add clinical value in determining hypoxic sub-regions.

Keywords: Cervix xenotransplants; GLUT-1 transporter; [18F]F-FAZA; [18F]F-FDG; hexokinase enzyme-II; hypoxia; hypoxia-inducible factor-1α (HIF-1α); ovarian xenotransplants; positron emission tomography (PET); preclinical.