Abstract | 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.
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Authors | Antoine Leimgruber, Kevin Hickson, Sze Ting Lee, Hui K Gan, Lawrence M Cher, John I Sachinidis, Graeme J O'Keefe, Andrew M Scott |
Journal | European journal of nuclear medicine and molecular imaging
(Eur J Nucl Med Mol Imaging)
Vol. 47
Issue 6
Pg. 1476-1485
(06 2020)
ISSN: 1619-7089 [Electronic] Germany |
PMID | 32025750
(Publication Type: Clinical Trial, Journal Article)
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Chemical References |
- Radiopharmaceuticals
- Fluorodeoxyglucose F18
- Misonidazole
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Topics |
- Aged
- Fluorodeoxyglucose F18
- Glioblastoma
(diagnostic imaging, radiotherapy)
- Glycolysis
- Humans
- Hypoxia
(diagnostic imaging)
- Middle Aged
- Misonidazole
- Neoplasm Recurrence, Local
(diagnostic imaging, radiotherapy)
- Positron-Emission Tomography
- Prospective Studies
- Radiopharmaceuticals
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