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DOI: 10.1055/s-0043-1769969
The Cancer-Associated Fibroblast and Hypoxia Nexus: Correlation between 68Ga-FAPI PET and Hypoxia Inducible Factor-1alpha Immunohistochemistry
kgomotso.mokoala@up.ac.za
Introduction: Cervical cancer lesions, like most solid tumors, grow large, and outgrow their blood supply which leads to hypoxia. Hypoxia has been shown to upregulate the presence and functions of cancer associated fibroblasts (CAFs) which results in increased aggressiveness. Hypoxia inducible factor-1α (HIF-1α) is a well-studied marker of hypoxia. PET imaging of gynecological cancers with 68Ga-FAPI has been documented. We aimed to utilize 68Ga-FAPI PET as a surrogate tracer of hypoxia and we correlated the imaging findings with immunohistochemical analysis of HIF-1α expression.
Methods: Women with histologically confirmed cervical cancer underwent both 18F-FDG PET/CT and 68Ga-FAPI PET/CT. Whole-body scan was acquired 60 minutes post tracer injection. Qualitative and semiquantitative analysis of tumor uptake was performed. We documented the following PET derived metrics of the primary lesion: maximum and mean standardized uptake value (SUVmax and SUVmean) and FAPI tumor volume (FAPI TV). We documented all extra cervical sites of 68Ga-FAPI uptake. Immunohistochemical staining and metastases were correlated to PET derived parameters.
Results: Eight of the thirteen women included had immunohistochemical analysis for HIF-1α expression. The mean age was 47 ± 12.76 years. There was primary cervical region or cervical bed region uptake in all patients. Lymph node metastases were seen in all the eight patients while only five patients had distant visceral or skeletal metastases. The mean SUVmax, SUVmean, and FAPI TV were 18.89, 6.88, and 195.66 cm3, respectively. Patients with additional sites of metastases had higher average FAPI-TV than those without. All tested samples demonstrated varying intensities of HIF-1α expression. There was a positive correlation between the FAPI-TV and the percentage distribution of HIF-1α staining. There was also a positive correlation between the presence of skeletal metastases and staining.
Conclusion: The FAPI-TV was correlated to the distribution of HIF-1 expression. Interestingly, the FAPI-TV was a higher in patients with metastatic disease. Larger studies are needed to confirm our findings.
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No conflict of interest has been declared by the author(s).
Publication History
Article published online:
25 May 2023
© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
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