The effect of the mTOR inhibitor rapamycin on glucoCEST signal in a preclinical model of glioblastoma

Xiang Xu, Jiadi Xu, Linda Knutsson, Jing Liu, Huanling Liu, Yuguo Li, Bachchu Lal, John J Laterra, Dmitri Artemov, Guanshu Liu, Peter C Van Zijl, Kannie W.Y. Chan

Research output: Contribution to journalArticle

Abstract

Purpose: The mammalian target of rapamycin is an enzyme that regulates cell metabolism and proliferation. It is up-regulated in aggressive tumors, such as glioblastoma, leading to increased glucose uptake and consumption. It has been suggested that glucose CEST signals reflect the delivery and tumor uptake of glucose. The inhibitor rapamycin (sirolimus) has been applied as a glucose deprivation treatment; thus, glucose CEST MRI could potentially be useful for monitoring the tumor responses to inhibitor treatment. Methods: A human U87-EGFRvIII xenograft model in mice was studied. The mice were treated with a mammalian target of Rapamycin inhibitor, rapamycin. The effect of the treatment was evaluated in vivo with dynamic glucose CEST MRI. Results: Rapamycin treatment led to significant increases (P < 0.001) in dynamic glucose-enhanced signal in both the tumor and contralateral brain as compared to the no-treatment group, namely a maximum enhancement of 3.7% ± 2.3% (tumor, treatment) versus 1.9% ± 0.4% (tumor, no-treatment), 1.7% ± 1.1% (contralateral, treatment), and 1.0% ± 0.4% (contralateral, no treatment). Dynamic glucose-enhanced contrast remained consistently higher in treatment versus no-treatment groups for the duration of the experiment (17 min). This was confirmed with area-under-curve analysis. Conclusion: Increased glucose CEST signal was found after mammalian target of Rapamycin inhibition treatment, indicating potential for dynamic glucose-enhanced MRI to study tumor response to glucose deprivation treatment.

Original languageEnglish (US)
JournalMagnetic resonance in medicine
DOIs
StatePublished - Jan 1 2019

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Sirolimus
Glioblastoma
Glucose
Neoplasms
Heterografts
Brain Neoplasms
Area Under Curve
Cell Proliferation

Keywords

  • DGE MRI
  • glioblastoma
  • glucoCEST
  • mTOR inhibitor
  • preclinical imaging
  • rapamycin

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

@article{98f34e42bda848238a673417f5a460b2,
title = "The effect of the mTOR inhibitor rapamycin on glucoCEST signal in a preclinical model of glioblastoma",
abstract = "Purpose: The mammalian target of rapamycin is an enzyme that regulates cell metabolism and proliferation. It is up-regulated in aggressive tumors, such as glioblastoma, leading to increased glucose uptake and consumption. It has been suggested that glucose CEST signals reflect the delivery and tumor uptake of glucose. The inhibitor rapamycin (sirolimus) has been applied as a glucose deprivation treatment; thus, glucose CEST MRI could potentially be useful for monitoring the tumor responses to inhibitor treatment. Methods: A human U87-EGFRvIII xenograft model in mice was studied. The mice were treated with a mammalian target of Rapamycin inhibitor, rapamycin. The effect of the treatment was evaluated in vivo with dynamic glucose CEST MRI. Results: Rapamycin treatment led to significant increases (P < 0.001) in dynamic glucose-enhanced signal in both the tumor and contralateral brain as compared to the no-treatment group, namely a maximum enhancement of 3.7{\%} ± 2.3{\%} (tumor, treatment) versus 1.9{\%} ± 0.4{\%} (tumor, no-treatment), 1.7{\%} ± 1.1{\%} (contralateral, treatment), and 1.0{\%} ± 0.4{\%} (contralateral, no treatment). Dynamic glucose-enhanced contrast remained consistently higher in treatment versus no-treatment groups for the duration of the experiment (17 min). This was confirmed with area-under-curve analysis. Conclusion: Increased glucose CEST signal was found after mammalian target of Rapamycin inhibition treatment, indicating potential for dynamic glucose-enhanced MRI to study tumor response to glucose deprivation treatment.",
keywords = "DGE MRI, glioblastoma, glucoCEST, mTOR inhibitor, preclinical imaging, rapamycin",
author = "Xiang Xu and Jiadi Xu and Linda Knutsson and Jing Liu and Huanling Liu and Yuguo Li and Bachchu Lal and Laterra, {John J} and Dmitri Artemov and Guanshu Liu and {Van Zijl}, {Peter C} and Chan, {Kannie W.Y.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1002/mrm.27683",
language = "English (US)",
journal = "Magnetic Resonance in Medicine",
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TY - JOUR

T1 - The effect of the mTOR inhibitor rapamycin on glucoCEST signal in a preclinical model of glioblastoma

AU - Xu, Xiang

AU - Xu, Jiadi

AU - Knutsson, Linda

AU - Liu, Jing

AU - Liu, Huanling

AU - Li, Yuguo

AU - Lal, Bachchu

AU - Laterra, John J

AU - Artemov, Dmitri

AU - Liu, Guanshu

AU - Van Zijl, Peter C

AU - Chan, Kannie W.Y.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Purpose: The mammalian target of rapamycin is an enzyme that regulates cell metabolism and proliferation. It is up-regulated in aggressive tumors, such as glioblastoma, leading to increased glucose uptake and consumption. It has been suggested that glucose CEST signals reflect the delivery and tumor uptake of glucose. The inhibitor rapamycin (sirolimus) has been applied as a glucose deprivation treatment; thus, glucose CEST MRI could potentially be useful for monitoring the tumor responses to inhibitor treatment. Methods: A human U87-EGFRvIII xenograft model in mice was studied. The mice were treated with a mammalian target of Rapamycin inhibitor, rapamycin. The effect of the treatment was evaluated in vivo with dynamic glucose CEST MRI. Results: Rapamycin treatment led to significant increases (P < 0.001) in dynamic glucose-enhanced signal in both the tumor and contralateral brain as compared to the no-treatment group, namely a maximum enhancement of 3.7% ± 2.3% (tumor, treatment) versus 1.9% ± 0.4% (tumor, no-treatment), 1.7% ± 1.1% (contralateral, treatment), and 1.0% ± 0.4% (contralateral, no treatment). Dynamic glucose-enhanced contrast remained consistently higher in treatment versus no-treatment groups for the duration of the experiment (17 min). This was confirmed with area-under-curve analysis. Conclusion: Increased glucose CEST signal was found after mammalian target of Rapamycin inhibition treatment, indicating potential for dynamic glucose-enhanced MRI to study tumor response to glucose deprivation treatment.

AB - Purpose: The mammalian target of rapamycin is an enzyme that regulates cell metabolism and proliferation. It is up-regulated in aggressive tumors, such as glioblastoma, leading to increased glucose uptake and consumption. It has been suggested that glucose CEST signals reflect the delivery and tumor uptake of glucose. The inhibitor rapamycin (sirolimus) has been applied as a glucose deprivation treatment; thus, glucose CEST MRI could potentially be useful for monitoring the tumor responses to inhibitor treatment. Methods: A human U87-EGFRvIII xenograft model in mice was studied. The mice were treated with a mammalian target of Rapamycin inhibitor, rapamycin. The effect of the treatment was evaluated in vivo with dynamic glucose CEST MRI. Results: Rapamycin treatment led to significant increases (P < 0.001) in dynamic glucose-enhanced signal in both the tumor and contralateral brain as compared to the no-treatment group, namely a maximum enhancement of 3.7% ± 2.3% (tumor, treatment) versus 1.9% ± 0.4% (tumor, no-treatment), 1.7% ± 1.1% (contralateral, treatment), and 1.0% ± 0.4% (contralateral, no treatment). Dynamic glucose-enhanced contrast remained consistently higher in treatment versus no-treatment groups for the duration of the experiment (17 min). This was confirmed with area-under-curve analysis. Conclusion: Increased glucose CEST signal was found after mammalian target of Rapamycin inhibition treatment, indicating potential for dynamic glucose-enhanced MRI to study tumor response to glucose deprivation treatment.

KW - DGE MRI

KW - glioblastoma

KW - glucoCEST

KW - mTOR inhibitor

KW - preclinical imaging

KW - rapamycin

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