Metabolic Response of Glioblastoma to Superselective Intra-Arterial Cerebral Infusion of Bevacizumab: A Proton MR Spectroscopic Imaging Study

Jeon, Jae Yong; Kovanlikaya, I.; Boockvar, John A.; Mao, Xiangling; Shin, Benjamin J.; Burkhardt, Jan Karl; Kesavabhotla, Kartik; Christos, Paul J.; Riina, Howard A.; Shungu, Dikoma C.; Tsiouris, Apostolos John

doi:10.3174/ajnr.a3091

Cited by 30 publications

(31 citation statements)

References 28 publications

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“…Choline-containing compounds are typically elevated in glioblastomas, while N-acetylaspartate (NAA), regarded as a neuronal marker, is decreased [15]. Interestingly, a decrease in the Choline/Creatine and an increase in the NAA/Choline ratios have been observed in patients treated with Bev [45], [46]. As Bev has no apparent impact on tumor cells in vitro , and does not modify overall survival in patients [11], these ratios are thus not reliable to assess direct drug cytotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Impact of Anti-Angiogenic Agents on U87 Glioma Cells

et al. 2014

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BackgroundGlioma cells not only secrete high levels of vascular endothelial growth factor (VEGF) but also express VEGF receptors (VEGFR), supporting the existence of an autocrine loop. The direct impact on glioma cells metabolism of drugs targeting the VEGF pathway, such as Bevacizumab (Bev) or VEGFR Tyrosine Kinase Inhibitor (TKI), is poorly known.Material and MethodsU87 cells were treated with Bev or SU1498, a selective VEGFR2 TKI. VEGFR expression was checked with FACS flow cytometry and Quantitative Real-Time PCR. VEGF secretion into the medium was assessed with an ELISA kit. Metabolomic studies on cells were performed using High Resolution Magic Angle Spinning Spectroscopy (HR-MAS).ResultsU87 cells secreted VEGF and expressed low level of VEGFR2, but no detectable VEGFR1. Exposure to SU1498, but not Bev, significantly impacted cell proliferation and apoptosis. Metabolomic studies with HR MAS showed that Bev had no significant effect on cell metabolism, while SU1498 induced a marked increase in lipids and a decrease in glycerophosphocholine. Accordingly, accumulation of lipid droplets was seen in the cytoplasm of SU1498-treated U87 cells.ConclusionAlthough both drugs target the VEGF pathway, only SU1498 showed a clear impact on cell proliferation, cell morphology and metabolism. Bevacizumab is thus less likely to modify glioma cells phenotype due to a direct therapeutic pressure on the VEGF autocrine loop. In patients treated with VEGFR TKI, monitoring lipids with magnetic resonance spectroscopic (MRS) might be a valuable marker to assess drug cytotoxicity.

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Section: Discussionmentioning

confidence: 99%

Metabolic Impact of Anti-Angiogenic Agents on U87 Glioma Cells

et al. 2014

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“…Recently, the use of MRSI has been reported for the monitoring of tumor response to intraarterial bevacizumab [ 99 ]. In this phase I trial, it appears that the Cho/NAA ratio may be helpful in monitoring tumor response (most tumors showed a decrease in Cho/NAA 3-5 weeks post treatment); however correlation with clinical or other measures of outcome was not performed.…”

Section: Treatment Planning and Monitoringmentioning

confidence: 93%

Diagnosis and Characterization of Brain Tumors: MR Spectroscopic Imaging

Barker

2013

Functional Brain Tumor Imaging

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“…The considerable excitement which greeted availability of Avastin, to test the long suspected hypothesis of Folkman for a central role of angiogenesis in active tumor growth, and the numerous prior MRS guided studies involving much less effective brain tumor therapies, makes the present reports [25,26] of great interest. While a total of only 32 patients were involved, these two studies fulfilled almost all of the tabulated criteria.…”

Section: Mrs Response Of Glioblastoma To Mannitol and Avastin (Bevacimentioning

confidence: 98%

High-field MRS in clinical drug development

Ross

2013

Expert Opinion on Drug Discovery

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MRS-guided drug discovery is poised for future expansion. The cost of clinical trials has escalated and the use of biomarkers has become increasingly useful in improving patient selection for drug trials. Clinical MRS has uncovered a treasure-trove of novel biomarkers and clinical MRS itself has become better standardized and more widely available on 'routine' clinical MRI scanners. When combined with available new MRI sequences, MRS can provide a 'one stop shop' with multiple potential outcome measures for the disease and the drug in question.

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Metabolic Response of Glioblastoma to Superselective Intra-Arterial Cerebral Infusion of Bevacizumab: A Proton MR Spectroscopic Imaging Study

Cited by 30 publications

References 28 publications

Metabolic Impact of Anti-Angiogenic Agents on U87 Glioma Cells

Metabolic Impact of Anti-Angiogenic Agents on U87 Glioma Cells

Diagnosis and Characterization of Brain Tumors: MR Spectroscopic Imaging

High-field MRS in clinical drug development

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