Multi-Aspect Optoacoustic Imaging of Breast Tumors under Chemotherapy with Exogenous and Endogenous Contrasts: Focus on Apoptosis and Hypoxia

Breast cancer is a complex tumor type involving many biological processes. Most chemotherapeutic agents exert their antitumoral effects by rapid induction of apoptosis. Another main feature of breast cancer is hypoxia, which may drive malignant progression and confer resistance to various forms of t...

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Autores principales:	Angelos Karlas, Antonio Nunes, Wouter Driessen, Evangelos Liapis, Josefine Reber
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	photoacoustics multispectral optoacoustic tomography MSOT breast cancer molecular imaging contrast agent Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ed9b1c86cc634aadbe6dd83fae600f46
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spelling	oai:doaj.org-article:ed9b1c86cc634aadbe6dd83fae600f462021-11-25T16:50:56ZMulti-Aspect Optoacoustic Imaging of Breast Tumors under Chemotherapy with Exogenous and Endogenous Contrasts: Focus on Apoptosis and Hypoxia10.3390/biomedicines91116962227-9059https://doaj.org/article/ed9b1c86cc634aadbe6dd83fae600f462021-11-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1696https://doaj.org/toc/2227-9059Breast cancer is a complex tumor type involving many biological processes. Most chemotherapeutic agents exert their antitumoral effects by rapid induction of apoptosis. Another main feature of breast cancer is hypoxia, which may drive malignant progression and confer resistance to various forms of therapy. Thus, multi-aspect imaging of both tumor apoptosis and oxygenation in vivo would be of enormous value for the effective evaluation of therapy response. Herein, we demonstrate the capability of a hybrid imaging modality known as multispectral optoacoustic tomography (MSOT) to provide high-resolution, simultaneous imaging of tumor apoptosis and oxygenation, based on both the exogenous contrast of an apoptosis-targeting dye and the endogenous contrast of hemoglobin. MSOT imaging was applied on mice bearing orthotopic 4T1 breast tumors before and following treatment with doxorubicin. Apoptosis was monitored over time by imaging the distribution of xPLORE-APOFL750©, a highly sensitive poly-caspase binding apoptotic probe, within the tumors. Oxygenation was monitored by tracking the distribution of oxy- and deoxygenated hemoglobin within the same tumor areas. Doxorubicin treatment induced an increase in apoptosis-depending optoacoustic signal of xPLORE-APOFL750© at 24 h after treatment. Furthermore, our results showed spatial correspondence between xPLORE-APO750© and deoxygenated hemoglobin. In vivo apoptotic status of the tumor tissue was independently verified by ex vivo fluorescence analysis. Overall, our results provide a rationale for the use of MSOT as an effective tool for simultaneously investigating various aspects of tumor pathophysiology and potential effects of therapeutic regimes based on both endogenous and exogenous molecular contrasts.Angelos KarlasAntonio NunesWouter DriessenEvangelos LiapisJosefine ReberMDPI AGarticlephotoacousticsmultispectral optoacoustic tomographyMSOTbreast cancermolecular imagingcontrast agentBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1696, p 1696 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	photoacoustics multispectral optoacoustic tomography MSOT breast cancer molecular imaging contrast agent Biology (General) QH301-705.5
spellingShingle	photoacoustics multispectral optoacoustic tomography MSOT breast cancer molecular imaging contrast agent Biology (General) QH301-705.5 Angelos Karlas Antonio Nunes Wouter Driessen Evangelos Liapis Josefine Reber Multi-Aspect Optoacoustic Imaging of Breast Tumors under Chemotherapy with Exogenous and Endogenous Contrasts: Focus on Apoptosis and Hypoxia
description	Breast cancer is a complex tumor type involving many biological processes. Most chemotherapeutic agents exert their antitumoral effects by rapid induction of apoptosis. Another main feature of breast cancer is hypoxia, which may drive malignant progression and confer resistance to various forms of therapy. Thus, multi-aspect imaging of both tumor apoptosis and oxygenation in vivo would be of enormous value for the effective evaluation of therapy response. Herein, we demonstrate the capability of a hybrid imaging modality known as multispectral optoacoustic tomography (MSOT) to provide high-resolution, simultaneous imaging of tumor apoptosis and oxygenation, based on both the exogenous contrast of an apoptosis-targeting dye and the endogenous contrast of hemoglobin. MSOT imaging was applied on mice bearing orthotopic 4T1 breast tumors before and following treatment with doxorubicin. Apoptosis was monitored over time by imaging the distribution of xPLORE-APOFL750©, a highly sensitive poly-caspase binding apoptotic probe, within the tumors. Oxygenation was monitored by tracking the distribution of oxy- and deoxygenated hemoglobin within the same tumor areas. Doxorubicin treatment induced an increase in apoptosis-depending optoacoustic signal of xPLORE-APOFL750© at 24 h after treatment. Furthermore, our results showed spatial correspondence between xPLORE-APO750© and deoxygenated hemoglobin. In vivo apoptotic status of the tumor tissue was independently verified by ex vivo fluorescence analysis. Overall, our results provide a rationale for the use of MSOT as an effective tool for simultaneously investigating various aspects of tumor pathophysiology and potential effects of therapeutic regimes based on both endogenous and exogenous molecular contrasts.
format	article
author	Angelos Karlas Antonio Nunes Wouter Driessen Evangelos Liapis Josefine Reber
author_facet	Angelos Karlas Antonio Nunes Wouter Driessen Evangelos Liapis Josefine Reber
author_sort	Angelos Karlas
title	Multi-Aspect Optoacoustic Imaging of Breast Tumors under Chemotherapy with Exogenous and Endogenous Contrasts: Focus on Apoptosis and Hypoxia
title_short	Multi-Aspect Optoacoustic Imaging of Breast Tumors under Chemotherapy with Exogenous and Endogenous Contrasts: Focus on Apoptosis and Hypoxia
title_full	Multi-Aspect Optoacoustic Imaging of Breast Tumors under Chemotherapy with Exogenous and Endogenous Contrasts: Focus on Apoptosis and Hypoxia
title_fullStr	Multi-Aspect Optoacoustic Imaging of Breast Tumors under Chemotherapy with Exogenous and Endogenous Contrasts: Focus on Apoptosis and Hypoxia
title_full_unstemmed	Multi-Aspect Optoacoustic Imaging of Breast Tumors under Chemotherapy with Exogenous and Endogenous Contrasts: Focus on Apoptosis and Hypoxia
title_sort	multi-aspect optoacoustic imaging of breast tumors under chemotherapy with exogenous and endogenous contrasts: focus on apoptosis and hypoxia
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/ed9b1c86cc634aadbe6dd83fae600f46
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_version_	1718412931420389376

Multi-Aspect Optoacoustic Imaging of Breast Tumors under Chemotherapy with Exogenous and Endogenous Contrasts: Focus on Apoptosis and Hypoxia

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