Intracellular Water Lifetime as a Tumor Biomarker to Monitor Doxorubicin Treatment via FFC-Relaxometry in a Breast Cancer Model

This study aims to explore whether the water exchange rate constants in tumor cells can act as a hallmark of pathology status and a reporter of therapeutic outcomes. It has been shown, using 4T1 cell cultures and murine allografts, that an early assessment of the therapeutic effect of doxorubicin ca...

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Autores principales:	Maria Rosaria Ruggiero, Simona Baroni, Valeria Bitonto, Roberto Ruiu, Smeralda Rapisarda, Silvio Aime, Simonetta Geninatti Crich
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	NMR relaxometry theranostics doxorubicin magnetic resonance imaging cellular water efflux rate constant Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/e704e27b3e7d4c89a99602ff6b0019b6
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spelling	oai:doaj.org-article:e704e27b3e7d4c89a99602ff6b0019b62021-12-03T06:00:53ZIntracellular Water Lifetime as a Tumor Biomarker to Monitor Doxorubicin Treatment via FFC-Relaxometry in a Breast Cancer Model2234-943X10.3389/fonc.2021.778823https://doaj.org/article/e704e27b3e7d4c89a99602ff6b0019b62021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.778823/fullhttps://doaj.org/toc/2234-943XThis study aims to explore whether the water exchange rate constants in tumor cells can act as a hallmark of pathology status and a reporter of therapeutic outcomes. It has been shown, using 4T1 cell cultures and murine allografts, that an early assessment of the therapeutic effect of doxorubicin can be detected through changes in the cellular water efflux rate constant kio. The latter has been estimated by analyzing the magnetization recovery curve in standard NMR T1 measurements when there is a marked difference in the proton relaxation rate constants (R1) between the intra- and the extra-cellular compartments. In cellular studies, T1 measurements were carried out on a relaxometer working at 0.5 T, and the required difference in R1 between the two compartments was achieved via the addition of a paramagnetic agent into the extracellular compartment. For in-vivo experiments, the large difference in the R1 values of the two-compartments was achieved when the T1 measurements were carried out at low magnetic field strengths. This task was accomplished using a Fast Field Cycling (FFC) relaxometer that was properly modified to host a mouse in its probe head. The decrease in kio upon the administration of doxorubicin is the result of the decreased activity of Na+/K+-ATPase, as shown in an independent test on the cellular uptake of Rb ions. The results reported herein suggest that kio can be considered a non-invasive, early and predictive biomarker for the identification of responsive patients immediately from the first doxorubicin treatment.Maria Rosaria RuggieroSimona BaroniValeria BitontoRoberto RuiuSmeralda RapisardaSilvio AimeSimonetta Geninatti CrichFrontiers Media S.A.articleNMR relaxometrytheranosticsdoxorubicinmagnetic resonance imagingcellular water efflux rate constantNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	NMR relaxometry theranostics doxorubicin magnetic resonance imaging cellular water efflux rate constant Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	NMR relaxometry theranostics doxorubicin magnetic resonance imaging cellular water efflux rate constant Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Maria Rosaria Ruggiero Simona Baroni Valeria Bitonto Roberto Ruiu Smeralda Rapisarda Silvio Aime Simonetta Geninatti Crich Intracellular Water Lifetime as a Tumor Biomarker to Monitor Doxorubicin Treatment via FFC-Relaxometry in a Breast Cancer Model
description	This study aims to explore whether the water exchange rate constants in tumor cells can act as a hallmark of pathology status and a reporter of therapeutic outcomes. It has been shown, using 4T1 cell cultures and murine allografts, that an early assessment of the therapeutic effect of doxorubicin can be detected through changes in the cellular water efflux rate constant kio. The latter has been estimated by analyzing the magnetization recovery curve in standard NMR T1 measurements when there is a marked difference in the proton relaxation rate constants (R1) between the intra- and the extra-cellular compartments. In cellular studies, T1 measurements were carried out on a relaxometer working at 0.5 T, and the required difference in R1 between the two compartments was achieved via the addition of a paramagnetic agent into the extracellular compartment. For in-vivo experiments, the large difference in the R1 values of the two-compartments was achieved when the T1 measurements were carried out at low magnetic field strengths. This task was accomplished using a Fast Field Cycling (FFC) relaxometer that was properly modified to host a mouse in its probe head. The decrease in kio upon the administration of doxorubicin is the result of the decreased activity of Na+/K+-ATPase, as shown in an independent test on the cellular uptake of Rb ions. The results reported herein suggest that kio can be considered a non-invasive, early and predictive biomarker for the identification of responsive patients immediately from the first doxorubicin treatment.
format	article
author	Maria Rosaria Ruggiero Simona Baroni Valeria Bitonto Roberto Ruiu Smeralda Rapisarda Silvio Aime Simonetta Geninatti Crich
author_facet	Maria Rosaria Ruggiero Simona Baroni Valeria Bitonto Roberto Ruiu Smeralda Rapisarda Silvio Aime Simonetta Geninatti Crich
author_sort	Maria Rosaria Ruggiero
title	Intracellular Water Lifetime as a Tumor Biomarker to Monitor Doxorubicin Treatment via FFC-Relaxometry in a Breast Cancer Model
title_short	Intracellular Water Lifetime as a Tumor Biomarker to Monitor Doxorubicin Treatment via FFC-Relaxometry in a Breast Cancer Model
title_full	Intracellular Water Lifetime as a Tumor Biomarker to Monitor Doxorubicin Treatment via FFC-Relaxometry in a Breast Cancer Model
title_fullStr	Intracellular Water Lifetime as a Tumor Biomarker to Monitor Doxorubicin Treatment via FFC-Relaxometry in a Breast Cancer Model
title_full_unstemmed	Intracellular Water Lifetime as a Tumor Biomarker to Monitor Doxorubicin Treatment via FFC-Relaxometry in a Breast Cancer Model
title_sort	intracellular water lifetime as a tumor biomarker to monitor doxorubicin treatment via ffc-relaxometry in a breast cancer model
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/e704e27b3e7d4c89a99602ff6b0019b6
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Intracellular Water Lifetime as a Tumor Biomarker to Monitor Doxorubicin Treatment via FFC-Relaxometry in a Breast Cancer Model

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