Abstract
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Objectives Although hypoxia in glioblastoma multiforme (GBM) may indicate tumor necrosis, it may also promote its proliferative activity by enhancing a number of relevant genes. Investigating intratumoral distribution of FDG and fluoromisonidazole (FMISO) allows assessment of hypoxic fraction in the hypermetabolic tissues, indicating anaerobic glycolysis. This study tried to correlate the hypoxic fraction with clinical growth parameters of GBM.
Methods GBM patients (N=13; 7 males; age 66±10 y.o.) underwent both FDG and FMISO PET using semiconductor PET (FWHM=2.3mm) before surgical resection or biopsy. Both FDG and FMISO PET images were analyzed on a pixel-by-pixel basis after software-based coregisteration to the individual MRI. Hypermetabolic pixel was defined as FDG-SUVR ≥ 1.0 to contralateral cortex, and hypoxic pixel was defined as FMISO-SUVR ≥ 1.3 to cerebellum. Hypoxic fraction in hypermetabolic volume was defined as [hypermetabolic & hypoxic volume] / [hypermetabolic volume]. Tumor growth parameters included 1) anatomical tumor volume on contrast-enhanced MRI, and 2) MIB-1 index, a pathological marker of tumor proliferation.
Results All the patients had hypermetabolic tumor tissue showing FDG-SUVRmax of 2.0±1.3 (range 1.1-5.7), and hypoxic tissue showing FMISO-SUVRmax of 3.5±0.5 (range 2.7-4.4). Mean hypermetabolic volume was 15±19 ml. Hypoxic fraction was estimated as 70±29% of hypermetabolic volume. Hypoxic fraction positively correlated with anatomical tumor volume (27±18 ml, Spearman's rank correlation coefficient ρ=0.74, P<0.01), but did not correlate with MIB-1 index (32±26%, range 5-100%, ρ=-0.29, P=NS).
Conclusions Hypoxic fraction positively correlated with anatomical tumor size, which indicates association of anaerobic glycolysis and tumor growth. Hypoxic fraction did not correlate with MIB-1 index, thus may represent an independent mechanism explaining aggressiveness of GBM.