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.

• Authors: Xiang Xu, Jiadi Xu, Linda Knutsson, Jing Liu, Huanling Liu, Yuguo Li, Bachchu Lal, John Laterra, Dmitri Artemov, Guanshu Liu, Peter C M van Zijl, Kannie W Y Chan
• Journal: Magnetic resonance in medicine (Magn Reson Med) Vol. 81 Issue 6 Pg. 3798-3807 (06 2019) ISSN: 1522-2594 [Electronic] United States
• PMID: 30793789 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 International Society for Magnetic Resonance in Medicine.

Chemical References

• Antibiotics, Antineoplastic
• Sirolimus

Topics

• Animals
• Antibiotics, Antineoplastic (pharmacology)
• Brain (diagnostic imaging, drug effects)
• Brain Chemistry (drug effects)
• Brain Neoplasms (diagnostic imaging, metabolism)
• Cell Line, Tumor
• Female
• Glioblastoma (diagnostic imaging, metabolism)
• Humans
• Magnetic Resonance Imaging
• Mice
• Mice, SCID
• Sirolimus (pharmacology)
• Xenograft Model Antitumor Assays