Assessing Metabolic Changes in Response to mTOR Inhibition in a Mantle Cell Lymphoma Xenograft Model Using AcidoCEST MRI
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 5...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publications
2016-04-01
|
| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.1177/1536012116645439 |
| _version_ | 1797288496118890496 |
|---|---|
| author | Paul J. Akhenblit PhD Neale T. Hanke PhD Alexander Gill BS Daniel O. Persky MD Christine M. Howison MS Mark D. Pagel PhD Amanda F. Baker PharmD, PhD |
| author_facet | Paul J. Akhenblit PhD Neale T. Hanke PhD Alexander Gill BS Daniel O. Persky MD Christine M. Howison MS Mark D. Pagel PhD Amanda F. Baker PharmD, PhD |
| author_sort | Paul J. Akhenblit PhD |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T18:50:20Z |
| format | Article |
| id | doaj.art-4f71f854ec3642e29acbf0ee34acba70 |
| institution | Directory Open Access Journal |
| issn | 1536-0121 |
| language | English |
| last_indexed | 2024-03-07T18:50:20Z |
| publishDate | 2016-04-01 |
| publisher | SAGE Publications |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj.art-4f71f854ec3642e29acbf0ee34acba702024-03-02T01:47:31ZengSAGE PublicationsMolecular Imaging1536-01212016-04-011510.1177/153601211664543910.1177_1536012116645439Assessing Metabolic Changes in Response to mTOR Inhibition in a Mantle Cell Lymphoma Xenograft Model Using AcidoCEST MRIPaul J. Akhenblit PhD0Neale T. Hanke PhD1Alexander Gill BS2Daniel O. Persky MD3Christine M. Howison MS4Mark D. Pagel PhD5Amanda F. Baker PharmD, PhD6 Cancer Biology Graduate Interdisciplinary Program, University of Arizona, Tucson, AZ, USA University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA Department of Medical Imaging, University of Arizona, Tucson, AZ, USA Department of Medical Imaging, University of Arizona, Tucson, AZ, USA University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USAAcidoCEST 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.https://doi.org/10.1177/1536012116645439 |
| spellingShingle | Paul J. Akhenblit PhD Neale T. Hanke PhD Alexander Gill BS Daniel O. Persky MD Christine M. Howison MS Mark D. Pagel PhD Amanda F. Baker PharmD, PhD Assessing Metabolic Changes in Response to mTOR Inhibition in a Mantle Cell Lymphoma Xenograft Model Using AcidoCEST MRI Molecular Imaging |
| title | Assessing Metabolic Changes in Response to mTOR Inhibition in a Mantle Cell Lymphoma Xenograft Model Using AcidoCEST MRI |
| title_full | Assessing Metabolic Changes in Response to mTOR Inhibition in a Mantle Cell Lymphoma Xenograft Model Using AcidoCEST MRI |
| title_fullStr | Assessing Metabolic Changes in Response to mTOR Inhibition in a Mantle Cell Lymphoma Xenograft Model Using AcidoCEST MRI |
| title_full_unstemmed | Assessing Metabolic Changes in Response to mTOR Inhibition in a Mantle Cell Lymphoma Xenograft Model Using AcidoCEST MRI |
| title_short | Assessing Metabolic Changes in Response to mTOR Inhibition in a Mantle Cell Lymphoma Xenograft Model Using AcidoCEST MRI |
| title_sort | assessing metabolic changes in response to mtor inhibition in a mantle cell lymphoma xenograft model using acidocest mri |
| url | https://doi.org/10.1177/1536012116645439 |
| work_keys_str_mv | AT pauljakhenblitphd assessingmetabolicchangesinresponsetomtorinhibitioninamantlecelllymphomaxenograftmodelusingacidocestmri AT nealethankephd assessingmetabolicchangesinresponsetomtorinhibitioninamantlecelllymphomaxenograftmodelusingacidocestmri AT alexandergillbs assessingmetabolicchangesinresponsetomtorinhibitioninamantlecelllymphomaxenograftmodelusingacidocestmri AT danieloperskymd assessingmetabolicchangesinresponsetomtorinhibitioninamantlecelllymphomaxenograftmodelusingacidocestmri AT christinemhowisonms assessingmetabolicchangesinresponsetomtorinhibitioninamantlecelllymphomaxenograftmodelusingacidocestmri AT markdpagelphd assessingmetabolicchangesinresponsetomtorinhibitioninamantlecelllymphomaxenograftmodelusingacidocestmri AT amandafbakerpharmdphd assessingmetabolicchangesinresponsetomtorinhibitioninamantlecelllymphomaxenograftmodelusingacidocestmri |