Imaging of Tumor Hypoxia With F-18-EF5 PET/MRI in Cervical Cancer

Purpose of the Report The aim of this study was to evaluate the distribution of hypoxia using F-18-EF5 as a hypoxia tracer in cervical cancer patients with PET/MRI. We investigated the association between this F-18-EF5-PET tracer and the immunohistochemical expression of endogenous hypoxia markers: HIF1 alpha, CAIX, and GLUT1. Patients and Methods Nine patients with biopsy-proven primary squamous cell cervix carcinoma (FIGO 2018 radiological stages IB1-IIIC2r) were imaged with dual tracers F-18-EF5 and F-18-FDG using PET/MRI (Int J Gynaecol Obstet. 2019;145:129-135). F-18-EF5 images were analyzed by calculating the tumor-to-muscle ratio to determine the hypoxic tissue (T/M ratio >1.5) and further hypoxic subvolume (HSV) and percentage hypoxic area. These F-18-EF5 hypoxic parameters were correlated with the size and localization of tumors in F-18-FDG PET/MRI and the results of hypoxia immunohistochemistry. Results All primary tumors were clearly F-18-FDG and F-18-EF5 PET positive and heterogeneously hypoxic with multiple F-18-EF5-avid areas in locally advanced cancer and single areas in clinically stage I tumors. The location of hypoxia was detected mainly in the periphery of tumor. Hypoxia parameters F-18-EF5 max T/M ratio and HSV in primary tumors correlated independently with the advanced stage (P = 0.036 and P = 0.040, respectively), and HSV correlated with the tumor size (P = 0.027). The location of hypoxia in F-18-EF5 imaging was confirmed with a higher hypoxic marker expression HIF1 alpha and CAIX in tumor fresh biopsies. Conclusions The F-18-EF5 imaging has promising potential in detecting areas of tumor hypoxia in cervical cancer.