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Phospholipid metabolites in recurrent glioblastoma: in vivo markers detect different tumor phenotypes before and under antiangiogenic therapy.
- Source :
-
PloS one [PLoS One] 2013; Vol. 8 (3), pp. e56439. Date of Electronic Publication: 2013 Mar 08. - Publication Year :
- 2013
-
Abstract
- Purpose: Metabolic changes upon antiangiogenic therapy of recurrent glioblastomas (rGBMs) may provide new biomarkers for treatment efficacy. Since in vitro models showed that phospholipid membrane metabolism provides specific information on tumor growth we employed in-vivo MR-spectroscopic imaging (MRSI) of human rGBMs before and under bevacizumab (BVZ) to measure concentrations of phosphocholine (PCho), phosphoethanolamine (PEth), glycerophosphocholine (GPC), and glyceroethanolamine (GPE).<br />Methods: (1)H and (31)P MRSI was prospectively performed in 32 patients with rGBMs before and under BVZ therapy at 8 weeks intervals until tumor progression. Patients were dichotomized into subjects with long overall survival (OS) (>median OS) and short OS (<median OS) survival time from BVZ-onset. Metabolite concentrations from tumor tissue and their ratios were compared to contralateral normal-appearing tissue (control).<br />Results: Before BVZ, (1)H-detectable choline signals (total GPC and PCho) in rGBMs were elevated but significance failed after dichotomizing. For metabolite ratios obtained by (31)P MRSI, the short-OS group showed higher PCho/GPC (p = 0.004) in rGBMs compared to control tissue before BVZ while PEth/GPE was elevated in rGBMs of both groups (long-OS p = 0.04; short-OS p = 0.003). Under BVZ, PCho/GPC and PEth/GPE in the tumor initially decreased (p = 0.04) but only PCho/GPC re-increased upon tumor progression (p = 0.02). Intriguingly, in normal-appearing tissue an initial PEth/GPE decrease (p = 0.047) was followed by an increase at the time of tumor progression (p = 0.031).<br />Conclusion: An elevated PCho/GPC ratio in the short-OS group suggests that it is a negative predictive marker for BVZ efficacy. These gliomas may represent a malignant phenotype even growing under anti-VEGF treatment. Elevated PEth/GPE may represent an in-vivo biomarker more sensitive to GBM infiltration than MRI.
- Subjects :
- Adult
Aged
Bevacizumab
Brain Neoplasms diagnostic imaging
Brain Neoplasms mortality
Disease-Free Survival
Female
Follow-Up Studies
Glioblastoma diagnostic imaging
Glioblastoma mortality
Humans
Magnetic Resonance Spectroscopy
Male
Middle Aged
Neoplasm Recurrence, Local diagnostic imaging
Neoplasm Recurrence, Local drug therapy
Neoplasm Recurrence, Local mortality
Prospective Studies
Radiography
Survival Rate
Angiogenesis Inhibitors administration & dosage
Antibodies, Monoclonal, Humanized administration & dosage
Brain Neoplasms drug therapy
Brain Neoplasms metabolism
Glioblastoma drug therapy
Glioblastoma metabolism
Neoplasm Recurrence, Local metabolism
Phospholipids metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23520454
- Full Text :
- https://doi.org/10.1371/journal.pone.0056439