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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/11/1696 |
| _version_ | 1797511179215568896 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:41:45Z |
| format | Article |
| id | doaj.art-ed9b1c86cc634aadbe6dd83fae600f46 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T05:41:45Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-ed9b1c86cc634aadbe6dd83fae600f462023-11-22T22:32:05ZengMDPI AGBiomedicines2227-90592021-11-01911169610.3390/biomedicines9111696Multi-Aspect Optoacoustic Imaging of Breast Tumors under Chemotherapy with Exogenous and Endogenous Contrasts: Focus on Apoptosis and HypoxiaAngelos Karlas0Antonio Nunes1Wouter Driessen2Evangelos Liapis3Josefine Reber4Chair of Biological Imaging, School of Medicine, Technical University of Munich, 81675 Munich, GermanyChair of Biological Imaging, School of Medicine, Technical University of Munich, 81675 Munich, GermanyiThera-Medical GmbH, 81379 Munich, GermanyChair of Biological Imaging, School of Medicine, Technical University of Munich, 81675 Munich, GermanyChair of Biological Imaging, School of Medicine, Technical University of Munich, 81675 Munich, GermanyBreast 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.https://www.mdpi.com/2227-9059/9/11/1696photoacousticsmultispectral optoacoustic tomographyMSOTbreast cancermolecular imagingcontrast agent |
| spellingShingle | 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 Biomedicines photoacoustics multispectral optoacoustic tomography MSOT breast cancer molecular imaging contrast agent |
| title | 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_short | 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 |
| topic | photoacoustics multispectral optoacoustic tomography MSOT breast cancer molecular imaging contrast agent |
| url | https://www.mdpi.com/2227-9059/9/11/1696 |
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