Concomitant [18F]F-FAZA and [18F]F-FDG Imaging of Gynecological Cancer Xenografts : Insight into Tumor Hypoxia
Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:38 |
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| Enthalten in: |
In vivo (Athens, Greece) - 38(2024), 2 vom: 27. März, Seite 574-586 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kepes, Zita [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 01.03.2024 Date Revised 04.03.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.21873/invivo.13476 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Concomitant [18F]F-FAZA and [18F]F-FDG Imaging of Gynecological Cancer Xenografts |b Insight into Tumor Hypoxia |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a CONCLUSION: The addition of [18F]F-FAZA PET to [18F]F-FGD imaging may add clinical value in determining hypoxic sub-regions | ||
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