Non-invasive imaging of disrupted protein homeostasis induced by proteasome inhibitor treatment using chemical exchange saturation transfer MRI

Abstract Proteasome inhibitors (PIs) are now standard of care for several cancers, and noninvasive biomarkers of treatment response are critically required for early patient stratification and treatment personalization. The present study evaluated whether chemical exchange (CEST) magnetic resonance...

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Autores principales:	Yanan Zhu, Rajiv Ramasawmy, Sean Peter Johnson, Valerie Taylor, Alasdair Gibb, R. Barbara Pedley, Nibedita Chattopadhyay, Mark F. Lythgoe, Xavier Golay, Daniel Bradley, Simon Walker-Samuel
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Chemical Exchange Saturation Transfer (CEST) Proteasome Inhibitor Treatment Disrupt Protein Homeostasis Ixazomib CEST Signal Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f8952b03910249259df62b0f5a1bc8a4
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spelling	oai:doaj.org-article:f8952b03910249259df62b0f5a1bc8a42021-12-02T15:09:12ZNon-invasive imaging of disrupted protein homeostasis induced by proteasome inhibitor treatment using chemical exchange saturation transfer MRI10.1038/s41598-018-33549-x2045-2322https://doaj.org/article/f8952b03910249259df62b0f5a1bc8a42018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-33549-xhttps://doaj.org/toc/2045-2322Abstract Proteasome inhibitors (PIs) are now standard of care for several cancers, and noninvasive biomarkers of treatment response are critically required for early patient stratification and treatment personalization. The present study evaluated whether chemical exchange (CEST) magnetic resonance imaging (MRI) can provide measurements that can be used as the noninvasive biomarkers of proteasome inhibition, alongside diffusion MRI and relaxometry. The sensitivity of human colorectal carcinoma cells to the PI Ixazomib was assessed via in vitro and in vivo dose-response experiments. Acute in vivo response to Ixazomib was assessed at three dosing concentrations, using CEST MRI (amide, amine, hydroxyl signals), diffusion MRI (ADC) and relaxometry (T1, T2). These responses were further evaluated with the known histological markers for Ixazomib and Bradford assay ex vivo. The CEST signal from amides and amines increased in proportion to Ixazomib dose in colorectal cancer xenografts. The cell lines differed in their sensitivity to Ixazomib, which was reflected in the MRI measurements. A mild stimulation in tumor growth was observed at low Ixazomib doses. Our results identify CEST MRI as a promising method for safely and noninvasively monitoring disrupted tumor protein homeostasis induced by proteasome inhibitor treatment, and for stratifying sensitivity between tumor types.Yanan ZhuRajiv RamasawmySean Peter JohnsonValerie TaylorAlasdair GibbR. Barbara PedleyNibedita ChattopadhyayMark F. LythgoeXavier GolayDaniel BradleySimon Walker-SamuelNature PortfolioarticleChemical Exchange Saturation Transfer (CEST)Proteasome Inhibitor TreatmentDisrupt Protein HomeostasisIxazomibCEST SignalMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Chemical Exchange Saturation Transfer (CEST) Proteasome Inhibitor Treatment Disrupt Protein Homeostasis Ixazomib CEST Signal Medicine R Science Q
spellingShingle	Chemical Exchange Saturation Transfer (CEST) Proteasome Inhibitor Treatment Disrupt Protein Homeostasis Ixazomib CEST Signal Medicine R Science Q Yanan Zhu Rajiv Ramasawmy Sean Peter Johnson Valerie Taylor Alasdair Gibb R. Barbara Pedley Nibedita Chattopadhyay Mark F. Lythgoe Xavier Golay Daniel Bradley Simon Walker-Samuel Non-invasive imaging of disrupted protein homeostasis induced by proteasome inhibitor treatment using chemical exchange saturation transfer MRI
description	Abstract Proteasome inhibitors (PIs) are now standard of care for several cancers, and noninvasive biomarkers of treatment response are critically required for early patient stratification and treatment personalization. The present study evaluated whether chemical exchange (CEST) magnetic resonance imaging (MRI) can provide measurements that can be used as the noninvasive biomarkers of proteasome inhibition, alongside diffusion MRI and relaxometry. The sensitivity of human colorectal carcinoma cells to the PI Ixazomib was assessed via in vitro and in vivo dose-response experiments. Acute in vivo response to Ixazomib was assessed at three dosing concentrations, using CEST MRI (amide, amine, hydroxyl signals), diffusion MRI (ADC) and relaxometry (T1, T2). These responses were further evaluated with the known histological markers for Ixazomib and Bradford assay ex vivo. The CEST signal from amides and amines increased in proportion to Ixazomib dose in colorectal cancer xenografts. The cell lines differed in their sensitivity to Ixazomib, which was reflected in the MRI measurements. A mild stimulation in tumor growth was observed at low Ixazomib doses. Our results identify CEST MRI as a promising method for safely and noninvasively monitoring disrupted tumor protein homeostasis induced by proteasome inhibitor treatment, and for stratifying sensitivity between tumor types.
format	article
author	Yanan Zhu Rajiv Ramasawmy Sean Peter Johnson Valerie Taylor Alasdair Gibb R. Barbara Pedley Nibedita Chattopadhyay Mark F. Lythgoe Xavier Golay Daniel Bradley Simon Walker-Samuel
author_facet	Yanan Zhu Rajiv Ramasawmy Sean Peter Johnson Valerie Taylor Alasdair Gibb R. Barbara Pedley Nibedita Chattopadhyay Mark F. Lythgoe Xavier Golay Daniel Bradley Simon Walker-Samuel
author_sort	Yanan Zhu
title	Non-invasive imaging of disrupted protein homeostasis induced by proteasome inhibitor treatment using chemical exchange saturation transfer MRI
title_short	Non-invasive imaging of disrupted protein homeostasis induced by proteasome inhibitor treatment using chemical exchange saturation transfer MRI
title_full	Non-invasive imaging of disrupted protein homeostasis induced by proteasome inhibitor treatment using chemical exchange saturation transfer MRI
title_fullStr	Non-invasive imaging of disrupted protein homeostasis induced by proteasome inhibitor treatment using chemical exchange saturation transfer MRI
title_full_unstemmed	Non-invasive imaging of disrupted protein homeostasis induced by proteasome inhibitor treatment using chemical exchange saturation transfer MRI
title_sort	non-invasive imaging of disrupted protein homeostasis induced by proteasome inhibitor treatment using chemical exchange saturation transfer mri
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/f8952b03910249259df62b0f5a1bc8a4
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Non-invasive imaging of disrupted protein homeostasis induced by proteasome inhibitor treatment using chemical exchange saturation transfer MRI

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