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

Xu, Xiang ; Xu, Jiadi ; Knutsson, Linda LU ; Liu, Jing ; Liu, Huanling ; Li, Yuguo ; Lal, Bachchu ; Laterra, John ; Artemov, Dmitri and Liu, Guanshu , et al. (2019) In Magnetic Resonance in Medicine 81(6). p.3798-3807
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... (More)

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.

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publication status
published
subject
keywords
DGE MRI, glioblastoma, glucoCEST, mTOR inhibitor, preclinical imaging, rapamycin
in
Magnetic Resonance in Medicine
volume
81
issue
6
pages
3798 - 3807
publisher
Wiley Online Library
external identifiers
  • scopus:85061986924
  • pmid:30793789
ISSN
0740-3194
DOI
10.1002/mrm.27683
language
English
LU publication?
yes
id
f0ffa60f-4a3e-4d19-afec-01501e8e9d63
date added to LUP
2019-03-07 14:43:55
date last changed
2019-12-06 03:00:28
@article{f0ffa60f-4a3e-4d19-afec-01501e8e9d63,
  abstract     = {<p>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 &lt; 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.</p>},
  author       = {Xu, Xiang and Xu, Jiadi and Knutsson, Linda and Liu, Jing and Liu, Huanling and Li, Yuguo and Lal, Bachchu and Laterra, John and Artemov, Dmitri and Liu, Guanshu and van Zijl, Peter C.M. and Chan, Kannie W.Y.},
  issn         = {0740-3194},
  language     = {eng},
  month        = {02},
  number       = {6},
  pages        = {3798--3807},
  publisher    = {Wiley Online Library},
  series       = {Magnetic Resonance in Medicine},
  title        = {The effect of the mTOR inhibitor rapamycin on glucoCEST signal in a preclinical model of glioblastoma},
  url          = {http://dx.doi.org/10.1002/mrm.27683},
  doi          = {10.1002/mrm.27683},
  volume       = {81},
  year         = {2019},
}