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

SIMPLE SUMMARY: Hypoxia is a phenomenon common in cervical cancer. Both the presence and function of CAFs are upregulated in a hypoxic environment. A key factor in the physiological response to hypoxia is hypoxia-inducible factor-1alpha (HIF-1 [Formula: see text]). We hypothesized that [(68)Ga]Ga-FAPI PET may be used as an indirect tracer for mapping hypoxia by correlating the image findings to pathological analysis of HIF-1 [Formula: see text] expression. The maximum and mean standardized uptake value (SUVmax and SUVmean) and FAPI tumor volume (FAPI-TV) were documented. There was uptake of tracer in the pelvis (cervix region) in all patients studied. All patients had lymph node metastases, while only six patients had distant visceral or skeletal metastases. The average FAPI-TV for patients with additional sites of metastases was higher than those without. Immunohistochemistry revealed varying intensities of HIF-1 [Formula: see text] expression in all tested samples. 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. ABSTRACT: 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-1 [Formula: see text]). [(68)Ga]Ga-FAPI PET imaging has been demonstrated in various cancer types. We hypothesized that [(68)Ga]Ga-FAPI PET may be used as an indirect tracer for mapping hypoxia by correlating the image findings to pathological analysis of HIF-1 [Formula: see text] expression. The [(68)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(3), respectively. The average FAPI-TV for patients with additional sites of metastases was higher than those without. Immunohistochemistry revealed varying intensities of HIF-1 [Formula: see text] expression in all tested samples. There was a positive correlation between the presence of skeletal metastases and staining for HIF-1 [Formula: see text]. 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.