PET is only moderately informative regarding theranostic Ttarget HIF-1α expression in solid tumors: A meta-analysis
Abstract BACKGROUND: Hypoxia-inducible factor (HIF)-1α plays a key role in hypoxic adaptation of tumor cells. HIF-1α is overexpressed in solid tumor, directs the glucose metabolism pathway from oxidative to anaerobic pathway thereby reducing the oxygen consumption, decreases free radical level and thence prevents cancer cell death. 2-deoxy-2 [18F] fluoro-D-glucose (FDG) is taken up in solid tumors primarily regulated through glucose transporter 1 (GLUT-1) and hexokinase 2 which in turn are regulated by HIF-1α. Positron Emission Tomography (PET) with FDG allows semiquantitative delineation of GLUT-1 and Hexokinase 2 activity in tumor cells by standardized uptake value (SUV). There are inconsistent data about relationships between FDG-PET and HIF-1a. The purpose of the present analysis was to provide evidence regarding associations between FDG uptake measured as standardized uptake value (SUV) and HIF-1α expression in solid tumors. METHODS: MEDLINE library, SCOPUS and EMBASE data bases were screened for relationships between SUVmax and HIF-1a up to August 2019. Overall, 21 studies with 1154 patients were identified. The following data were extracted from the literature: authors, year of publication, number of patients, and correlation coefficients. RESULTS: Correlation coefficients between SUV and HIF-1α ranged from -0.51 to 0.71. The pooled correlation coefficient was 0.27, (95% CI = [0.14; 0.41]). Furthermore, correlation coefficients for specific tumor entities were calculated. For this sub-analysis, data for primary tumors with more than two reports were included. The calculated correlation coefficients in the analyzed subgroups were as follows: head and neck squamous cell carcinoma: ρ = 0.25 (95% CI = [0.07; 0.42]); non-small lung cell cancer: ρ = 0.27 (95% CI = [-0.14; 0.67]); uterine cervical cancer: ρ = -0.09 (95% CI = [- 0.89; 0.71]); thymic tumors: ρ = 0.39 (95% CI = [0.04; 0.58]) CONCLUSION: Published literature suggests wide heterogeneity and weak correlation between intensity of FDG uptake measured as SUVmax and expression of HIF-1a both in solid tumors in general and also in specific tumor subgroups. Because HIF-1α is a very important theranostic target, prospective state of the art studies are needed to elucidate the true potential of FDG PET in assessment of HIF-1α activity in solid tumors