title: Assessing Metabolic Changes in Response to mTOR Inhibition in a Mantle Cell Lymphoma Xenograft Model Using AcidoCEST MRI.
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.
authors.affiliation: Cancer Biology Graduate Interdisciplinary Program, University of Arizona, Tucson, AZ, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Akhenblit
authors.affiliation: University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
authors.forename: Neale T
authors.initials: NT
authors.lastname: Hanke
authors.affiliation: University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Gill
authors.affiliation: University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Persky
authors.affiliation: Department of Medical Imaging, University of Arizona, Tucson, AZ, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Howison
authors.affiliation: Cancer Biology Graduate Interdisciplinary Program, 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.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Pagel
authors.affiliation: University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA abaker@uacc.arizona.edu.
authors.forename: Amanda F
authors.initials: AF
authors.lastname: Baker
mesh_terms: D000138:Acidosis / Q000000981:diagnostic imaging* / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000068338:Everolimus / Q000008:administration & dosage* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D020522:Lymphoma, Mantle-Cell / Q000737:chemistry / Q000188:drug therapy* / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D057054:Molecular Imaging / Q000379:methods; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000068338:Everolimus; D058570:TOR Serine-Threonine Kinases
keywords: CEST MRI; extracellular pH; lymphoma; mTOR inhibition; therapy response