Spatial and quantitative mapping of glycolysis and hypoxia in glioblastoma as a predictor of radiotherapy response and sites of relapse.

Introduction: Tumor hypoxia is a centerpiece of disease progression mechanisms such as neoangiogenesis or aggressive hypoxia-resistant malignant cells selection that impacts on radiotherapy strategies. Early identification of regions at risk for recurrence and prognostic-based classification of pati...

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Publicado en:European Journal of Nuclear Medicine & Molecular Imaging Vol. 47; no. 6; pp. 1476 - 1486
Autores principales: Leimgruber, Antoine, Hickson, Kevin, Lee, Sze Ting, Gan, Hui K, Cher, Lawrence M, Sachinidis, John I, O'Keefe, Graeme J, Scott, Andrew M
Formato: Journal Article
Publicado: Springer Nature Jun2020
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Jun2020
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s00259-020-04706-0
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        atl: Spatial and quantitative mapping of glycolysis and hypoxia in glioblastoma as a predictor of radiotherapy response and sites of relapse.
      aug:
        au:
          Leimgruber, Antoine
          Hickson, Kevin
          Lee, Sze Ting
          Gan, Hui K
          Cher, Lawrence M
          Sachinidis, John I
          O'Keefe, Graeme J
          Scott, Andrew M
        affil: Department of Molecular Imaging and Therapy, Austin Health, Heidelberg, Victoria, Australia
      sug:
      ab: Introduction: Tumor hypoxia is a centerpiece of disease progression mechanisms such as neoangiogenesis or aggressive hypoxia-resistant malignant cells selection that impacts on radiotherapy strategies. Early identification of regions at risk for recurrence and prognostic-based classification of patients is a necessity to devise tailored therapeutic strategies. We developed an image-based algorithm to spatially map areas of aerobic and anaerobic glycolysis (Glyoxia). Methods: 18F-FDG and 18F-FMISO PET studies were used in the algorithm to produce DICOM-co-registered representations and maximum intensity projections combined with quantitative analysis of hypoxic volume (HV), hypoxic glycolytic volume (HGV), and anaerobic glycolytic volume (AGV) with CT/MRI co-registration. This was applied to a prospective clinical trial of 10 glioblastoma patients with post-operative, pre-radiotherapy, and early post-radiotherapy 18F-FDG and 18F-FMISO PET and MRI studies. Results: In the 10 glioblastoma patients (5M:5F; age range 51–69 years), 14/18 18F-FMISO PET studies showed detectable hypoxia. Seven patients survived to complete post-radiotherapy studies. The patient with the longest overall survival showed non-detectable hypoxia in both pre-radiotherapy and post-radiotherapy 18F-FMISO PET. The three patients with increased HV, HGV, and AGV volumes after radiotherapy showed 2.8 months mean progression-free interval vs. 5.9 months for the other 4 patients. These parameters correlated at that time point with progression-free interval. Parameters combining hypoxia and glycolytic information (i.e., HGV and AGV) showed more prominent variation than hypoxia-based information alone (HV). Glyoxia-generated images were consistent with disease relapse topology; in particular, one patient had distant relapse anticipated by HV, HGV, and AGV maps. Conclusion: Spatial mapping of aerobic and anaerobic glycolysis allows unique information on tumor metabolism and hypoxia to be evaluated with PET, providing a greater understanding of tumor biology and potential response to therapy.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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