Correlation between [ 68 Ga]Ga-FAPI-46 PET Imaging and HIF-1α Immunohistochemical Analysis in Cervical Cancer: Proof-of-Concept

• Published in: Cancers Vol. 15; no. 15; p. 3953
• Main Authors: Mokoala, Kgomotso M G, Lawal, Ismaheel O, Maserumule, Letjie C, Bida, Meshack, Maes, Alex, Ndlovu, Honest, Reed, Janet, Mahapane, Johncy, Davis, Cindy, Van de Wiele, Christophe, Popoola, Gbenga, Giesel, Frederik L, Vorster, Mariza, Sathekge, Mike M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03-08-2023; MDPI
• Subjects: Cervical cancer; Cervix; Correlation analysis; Disease; Fibroblasts; Growth factors; Gynecology; HIV; Human immunodeficiency virus; Hypoxia; Hypoxia-inducible factor 1; Hypoxia-inducible factor 1a; Image processing; Immunohistochemistry; Lymph nodes; Lymphatic system; Mapping; Medical imaging; Medical research; Metastases; Metastasis; Ovarian cancer; Patients; Pelvis; Tumor microenvironment; Tumors; Variables; United States > US; [68Ga]Ga-FAPI PET/CT; HIF-1α; FAPI-TV; immunohistochemistry; cervical cancer
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers15153953

Hypoxia leads to changes in tumor microenvironment (upregulated CAFs) with resultant aggressiveness. A key factor in the physiological response to hypoxia is hypoxia-inducible factor-1alpha (HIF-1α). [
Ga]Ga-FAPI PET imaging has been demonstrated in various cancer types. We hypothesized that [
Ga]Ga-FAPI PET may be used as an indirect tracer for mapping hypoxia by correlating the image findings to pathological analysis of HIF-1α expression. The [
Ga]Ga-FAPI PET/CT scans of women with cancer of the cervix were reviewed and the maximum and mean standardized uptake value (SUVmax and SUVmean) and FAPI tumor volume (FAPI-TV) were documented. Correlation analysis was performed between PET-derived parameters and immunohistochemical staining as well as between PET-derived parameters and the presence of metastasis. Ten women were included. All patients demonstrated tracer uptake in the primary site or region of the primary. All patients had lymph node metastases while only six patients had distant visceral or skeletal metastases. The mean SUVmax, SUVmean, and FAPI-TV was 18.89, 6.88, and 195.66 cm
, respectively. The average FAPI-TV for patients with additional sites of metastases was higher than those without. Immunohistochemistry revealed varying intensities of HIF-1α expression in all tested samples. There was a positive correlation between the presence of skeletal metastases and staining for HIF-1α (r=0.80;p=0.017). The presence of skeletal metastasis was correlated to the HIF-1⍺ staining (percentage distribution). Furthermore, the FAPI-TV was a better predictor of metastatic disease than the SUVmax.