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

• Published in: In vivo (Athens) Vol. 38; no. 2; pp. 574 - 586
• Main Authors: Kepes, Zita, Hegedus, Eva, Sass, Tamas, Csikos, Csaba, Szabo, Judit P, Szugyiczki, Viktoria, Hajdu, István, Kertesz, Istvan, Opposits, Gabor, Imrek, Jozsef, Balkay, Laszlo, Kalman, Ferenc Krisztián, Trencsenyi, Gyorgy
• Format: Journal Article
• Language: English
• Published: Greece International Institute of Anticancer Research 01.03.2024
• Subjects: Animals; Cell Line, Tumor; Cobalt; Female; Fluorodeoxyglucose F18; Heterografts; Humans; Hypoxia - diagnostic imaging; Mice; Ovarian Neoplasms - diagnostic imaging; Positron-Emission Tomography - methods; Radiopharmaceuticals; Tumor Hypoxia; hypoxia; hypoxia-inducible factor-1α (HIF-1α); [18F]F-FAZA; [18F]F-FDG; Cervix xenotransplants; hexokinase enzyme-II; positron emission tomography (PET); preclinical; GLUT-1 transporter; ovarian xenotransplants
• ISSN: 0258-851X; 1791-7549
• DOI: 10.21873/invivo.13476

Herein we assessed the feasibility of imaging protocols using both hypoxia-specific [ F]F-FAZA and [ F]F-FDG in bypassing the limitations derived from the non-specific findings of [ F]F-FDG PET imaging of tumor-related hypoxia. CoCl -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]F-FDG/[ F]F-FAZA-based MiniPET imaging, in vitro [ F]F-FDG uptake measurements and western blotting were used to verify the presence of hypoxia. Elevated GLUT-1, and hexokinase enzyme-II expression driven by CoCl -induced activation of hypoxia-inducible factor-1α explains enhanced cellular [ F]F-FDG accumulation. No difference was observed in the [ F]F-FAZA accretion of Pgp+ and Pgp- tumors. Tumor-to-muscle ratios for [ F]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]F-FAZA between the tracer avid and non-accumulating regions indicate its superiority over [ F]F-FDG. Spatial correlation between [ F]F-FGD and [ F]F-FAZA scans confirms that hypoxia mostly occurs in regions with highly active glucose metabolism. The addition of [ F]F-FAZA PET to [ F]F-FGD imaging may add clinical value in determining hypoxic sub-regions.