NIMG-36. AMINO ACID METABOLISM MEASURED BY PET IS ASSOCIATED WITH SPECIFIC MOLECULAR BIOMARKERS IN PRIMARY GLIOBLASTOMA

Abstract

BACKGROUND: Several molecular markers were shown to provide prognostic information in glioblastomas. Among these, high Ki-67 nuclear labeling index (characterizing tumoral proliferative activity) and overexpression of epidermal growth factor receptor (EGFR) carry an unfavorable prognosis, while O-6-methylguanine-DNA methyltransferase (MGMT) promoter hypermethylation and isocitrate dehydrogenase 1 (IDH1) mutation are associated with longer survival. Some of these molecular markers may be associated with specific imaging characteristics including abnormal tumoral amino acid metabolism measured by positron emission tomography (PET). We have previously demonstrated increased transport and metabolic rates of tryptophan in malignant gliomas by alpha[11C]-L-methyl-tryptophan (AMT) PET. In the present study, we evaluated if prognostic molecular markers are associated with tryptophan transport and metabolic rates measured by AMT-PET in newly-diagnosed glioblastomas. METHODS: Twenty two patients (15 males, mean age: 62 years) with a suspected glioblastoma underwent presurgical imaging including dynamic AMT-PET following tumor resection and standard postsurgical chemoradiation. Tumoral tryptophan uptake on PET was measured by standardized uptake values (SUV), and kinetic PET parameters were also calculated to estimate tumoral tryptophan transport and metabolism and their tumor/cortex ratios. These PET parameters were correlated with molecular tumor markers. RESULTS: In all 22 patients, histopathology confirmed WHO grade IV glioma with wild type IDH consistent with primary glioblastoma. Mean Ki-67 labeling index was 30% (range: 10-70%). Tumors with MGMT promoter hypermethylation showed lower tumor/cortex AMT metabolic ratios than those with unmethylated MGMT (mean: 1.4 ± 0.5 vs. 2.0 ± 0.6, p=0.03), while high EGFR copy number was associated with elevated Ki-67 labeling index (45 ± 14% vs. 22 ± 6% in low-EGFR tumors, p<0.001), high tumoral tryptophan transport rates (tumor/cortex ratio: 3.6 ± 1.2 vs. 2.4 ± 1.1, p=0.05), and high SUVs (5.8 ± 1.9 vs. 4.6 ± 1.1, p=0.07). CONCLUSIONS: Tryptophan transport and metabolic rates, measured by PET, are associated with specific prognostic molecular markers (EGFR gene amplification and MGMT promoter methylation, respectively) in IDH wild-type glioblastoma.