18f-Faza Pet/Ct For Pre-Treatment Assessment Of Hypoxic Status In High Grade Glioma: Correlation With Hypoxia Immunohistochemical Markers

145 Aim: Positron emission Tomography/Computed Tomography (PET/CT) with 18F-FAZA is a valuable non-invasive method to investigate tumour hypoxia. Aim of the present study is to investigate the likelihood of a correlation between 18F-FAZA imaging data and hypoxia immunohistochemical markers in patients with high-grade glioma (HGG) Patients and Methods. Prospective single Centre clinical study. Eighteen patients with brain MRI suggestive for HGG have been enrolled and underwent pre-treatment 18F-FAZA PET/CT (2/18: FAZA not performed for tracer synthesis failure). The following 18F-FAZA PET-derived parameters have been considered for each scan:maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean) and metabolic tumour volume (MTV) at different thresholds of 40%, 50%, 60% (40-50-60), hypoxic volume (HV) estimated by applying different positivity thresholds to tumour to blood ratio (1.2, 1.3, 1.4), thus obtaining HV1.2, HV1.3; HV1.4. Ten out of 18 pts underwent stereotactic biopsy and 8/10 underwent craniotomy with surgical excision of the lesion. For each patient immunohistochemical analysis on the most representative tumor section were performed by considering the following markers: hypoxia inducible factor 1α [HIF-1α], Carboxic Anidrase IX [CA-IX] and Glucose Transporter-1 [GLUT-1]; tumor angiogenesis and proliferative index have been evaluated. Anti CA-IX, GLUT-1 and HIF-1α antibodies have been used a semiquantitative scoring system with five categories (0=0%, 1\u003c10%, 2=11-25%, 3=26-50% and 4=51-75%) has been applied to evaluate the extent of their expression. Anti-CD31 antibody has been used to assess tumour vascularity and Ki-67 to evaluate tumour proliferation. Evaluation of immunomarkers expression was independently performed by two expert pathologists blinded to PET results analysis. All PET-derived parameters were evaluated and compared with anatomopathological features. Results: 18F-FAZA showed one lesion in 16/18 patients and multiple lesions in 2/18 patients. According to World Health Organization (WHO) classification, 12/18 patients had grade IV glioma, 5/18 had grade II glioma and 1/18 was a brain metastases from lung cancer, therefore immunohistochemistry for hypoxia biomarker have been performed considering 17 patients. For HIF-1 α the following score/number of patients have been observed: 0/1, 1/15, 2/1. For CA-IX: 0/3, 1/8, 2/2, 3/3 and 4/1. Finally, for GLUT-1, 0/1,1/2, 2/6, 3/6 and 4/2 have been observed. Mean Ki-67 value was 19% (range: 3-40%). For hypoxia, vascluarization and proliferation assessment, bioptical and surgical samples have been considered separately for the analysis. In the surgical subgroup (n=7) CA-IX was correlated to all PET-derived parameters as follow: SUVmax (p=0.0002), SUVmean40 (p=0.0058); SUVmean50 (p=0.009), SUVmean60 (p=0.0153), MTV40-50-60 (p=0.0424), HV 1.2-1.3-1.4 (p=0.0058). In the bioptic subgroup (n=10) SUVmax (p=0.0094), SUVmean40(p=0.0107), SUVmean50 (p=0.0094), SUVmean60 (p=0.0154) were correlated with tumour vascularization. Conclusions: 18F-FAZA PET/CT can be a reliable method for assessing tumour hypoxia in HGG as supported by the correlation between imaging parameters and CA-IX and vascularization. The methodological need of subdividing the population into surgical and bioptical specimens might have hampered the statistical power of the study, although it has been necessary to guarantee homogeneity within each population.