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Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer

PURPOSE: The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer. PROCEDURES: CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated i...

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Autores principales: van Brussel, Aram S. A., Adams, Arthur, Oliveira, Sabrina, Dorresteijn, Bram, El Khattabi, Mohamed, Vermeulen, Jeroen F., van der Wall, Elsken, Mali, Willem P. Th. M., Derksen, Patrick W. B., van Diest, Paul J., van Bergen en Henegouwen, Paul M. P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927611/
https://www.ncbi.nlm.nih.gov/pubmed/26589824
http://dx.doi.org/10.1007/s11307-015-0909-6
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author van Brussel, Aram S. A.
Adams, Arthur
Oliveira, Sabrina
Dorresteijn, Bram
El Khattabi, Mohamed
Vermeulen, Jeroen F.
van der Wall, Elsken
Mali, Willem P. Th. M.
Derksen, Patrick W. B.
van Diest, Paul J.
van Bergen en Henegouwen, Paul M. P.
author_facet van Brussel, Aram S. A.
Adams, Arthur
Oliveira, Sabrina
Dorresteijn, Bram
El Khattabi, Mohamed
Vermeulen, Jeroen F.
van der Wall, Elsken
Mali, Willem P. Th. M.
Derksen, Patrick W. B.
van Diest, Paul J.
van Bergen en Henegouwen, Paul M. P.
author_sort van Brussel, Aram S. A.
collection PubMed
description PURPOSE: The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer. PROCEDURES: CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated in a xenograft breast cancer mouse model using ductal carcinoma in situ cells (DCIS). RESULTS: Specific anti-CAIX nanobodies were obtained. Administration of a CAIX-specific nanobody into mice with DCIS xenografts overexpressing CAIX showed after 2 h a mean tumor-to-normal tissue ratio (TNR) of 4.3 ± 0.6, compared to a TNR of 1.4 ± 0.2 in mice injected with the negative control nanobody R2-IR. In DCIS mice, a TNR of 1.8 ± 0.1 was obtained. Biodistribution studies demonstrated an uptake of 14.0 ± 1.1 %I.D./g in DCIS + CAIX tumors, 4.6 ± 0.8 %I.D./g in DCIS tumors, while 2.0 ± 0.2 %I.D./g was obtained with R2-IR. CONCLUSIONS: These results demonstrate the successful generation of a CAIX-specific nanobody-IRDye800CW conjugate that can be used for rapid imaging of (pre-)invasive breast cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11307-015-0909-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-49276112016-07-13 Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer van Brussel, Aram S. A. Adams, Arthur Oliveira, Sabrina Dorresteijn, Bram El Khattabi, Mohamed Vermeulen, Jeroen F. van der Wall, Elsken Mali, Willem P. Th. M. Derksen, Patrick W. B. van Diest, Paul J. van Bergen en Henegouwen, Paul M. P. Mol Imaging Biol Research Article PURPOSE: The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer. PROCEDURES: CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated in a xenograft breast cancer mouse model using ductal carcinoma in situ cells (DCIS). RESULTS: Specific anti-CAIX nanobodies were obtained. Administration of a CAIX-specific nanobody into mice with DCIS xenografts overexpressing CAIX showed after 2 h a mean tumor-to-normal tissue ratio (TNR) of 4.3 ± 0.6, compared to a TNR of 1.4 ± 0.2 in mice injected with the negative control nanobody R2-IR. In DCIS mice, a TNR of 1.8 ± 0.1 was obtained. Biodistribution studies demonstrated an uptake of 14.0 ± 1.1 %I.D./g in DCIS + CAIX tumors, 4.6 ± 0.8 %I.D./g in DCIS tumors, while 2.0 ± 0.2 %I.D./g was obtained with R2-IR. CONCLUSIONS: These results demonstrate the successful generation of a CAIX-specific nanobody-IRDye800CW conjugate that can be used for rapid imaging of (pre-)invasive breast cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11307-015-0909-6) contains supplementary material, which is available to authorized users. Springer US 2015-11-20 2016 /pmc/articles/PMC4927611/ /pubmed/26589824 http://dx.doi.org/10.1007/s11307-015-0909-6 Text en © The Author(s) 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Research Article
van Brussel, Aram S. A.
Adams, Arthur
Oliveira, Sabrina
Dorresteijn, Bram
El Khattabi, Mohamed
Vermeulen, Jeroen F.
van der Wall, Elsken
Mali, Willem P. Th. M.
Derksen, Patrick W. B.
van Diest, Paul J.
van Bergen en Henegouwen, Paul M. P.
Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer
title Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer
title_full Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer
title_fullStr Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer
title_full_unstemmed Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer
title_short Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer
title_sort hypoxia-targeting fluorescent nanobodies for optical molecular imaging of pre-invasive breast cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927611/
https://www.ncbi.nlm.nih.gov/pubmed/26589824
http://dx.doi.org/10.1007/s11307-015-0909-6
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