Assessing Metabolic Changes in Response to mTOR Inhibition in a Mantle Cell Lymphoma Xenograft Model Using AcidoCEST MRI

Paul J. Akhenblit, Neale T. Hanke, Alexander Gill, Daniel O. Persky, Christine M. Howison, Mark "Marty" Pagel, Amanda F Baker

Research output: Contribution to journalArticle

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Abstract

AcidoCEST magnetic resonance imaging (MRI) has previously been shown to measure tumor extracellular pH (pHe) with excellent accuracy and precision. This study investigated the ability of acidoCEST MRI to monitor changes in tumor pHe in response to therapy. To perform this study, we used the Granta 519 human mantle cell lymphoma cell line, which is an aggressive B-cell malignancy that demonstrates activation of the phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin (mTOR) pathway. We performed in vitro and in vivo studies using the Granta 519 cell line to investigate the efficacy and associated changes induced by the mTOR inhibitor, everolimus (RAD001). AcidoCEST MRI studies showed a statistically significant increase in tumor pHe of 0.10 pH unit within 1 day of initiating treatment, which foreshadowed a decrease in tumor growth of the Granta 519 xenograft model. AcidoCEST MRI then measured a decrease in tumor pHe 7 days after initiating treatment, which foreshadowed a return to normal tumor growth rate. Therefore, this study is a strong example that acidoCEST MRI can be used to measure tumor pHe that may serve as a marker for therapeutic efficacy of anticancer therapies.

Original languageEnglish (US)
JournalMolecular Imaging
Volume15
DOIs
StatePublished - 2016

Fingerprint

Mantle-Cell Lymphoma
Magnetic resonance
Heterografts
magnetic resonance
Tumors
Earth mantle
tumors
Magnetic Resonance Imaging
Imaging techniques
cells
Neoplasms
Cells
cultured cells
therapy
Phosphatidylinositol 3-Kinase
Cell Line
markers
inhibitors
Sirolimus
Growth

Keywords

  • CEST MRI
  • extracellular pH
  • lymphoma
  • mTOR inhibition
  • therapy response

ASJC Scopus subject areas

  • Biotechnology
  • Medicine(all)
  • Biomedical Engineering
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Condensed Matter Physics

Cite this

Assessing Metabolic Changes in Response to mTOR Inhibition in a Mantle Cell Lymphoma Xenograft Model Using AcidoCEST MRI. / Akhenblit, Paul J.; Hanke, Neale T.; Gill, Alexander; Persky, Daniel O.; Howison, Christine M.; Pagel, Mark "Marty"; Baker, Amanda F.

In: Molecular Imaging, Vol. 15, 2016.

Research output: Contribution to journalArticle

Akhenblit, Paul J. ; Hanke, Neale T. ; Gill, Alexander ; Persky, Daniel O. ; Howison, Christine M. ; Pagel, Mark "Marty" ; Baker, Amanda F. / Assessing Metabolic Changes in Response to mTOR Inhibition in a Mantle Cell Lymphoma Xenograft Model Using AcidoCEST MRI. In: Molecular Imaging. 2016 ; Vol. 15.
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