Use of a single hybrid imaging agent for integration of target validation with in vivo and ex vivo imaging of mouse tumor lesions resembling human DCIS.

<h4>Unlabelled</h4>Screening of biomarker expression levels in tumor biopsy samples not only provides an assessment of prognostic and predictive factors, but may also be used for selection of biomarker-specific imaging strategies. To assess the feasibility of using a biopsy specimen for...

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Autores principales: Tessa Buckle, Joeri Kuil, Nynke S van den Berg, Anton Bunschoten, Hildo J Lamb, Hushan Yuan, Lee Josephson, Jos Jonkers, Alexander D Borowsky, Fijs W B van Leeuwen
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:f6d330fe80da41a880a60b08992a5acf2021-11-18T08:01:55ZUse of a single hybrid imaging agent for integration of target validation with in vivo and ex vivo imaging of mouse tumor lesions resembling human DCIS.1932-620310.1371/journal.pone.0048324https://doaj.org/article/f6d330fe80da41a880a60b08992a5acf2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23326303/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Unlabelled</h4>Screening of biomarker expression levels in tumor biopsy samples not only provides an assessment of prognostic and predictive factors, but may also be used for selection of biomarker-specific imaging strategies. To assess the feasibility of using a biopsy specimen for a personalized selection of an imaging agent, the chemokine receptor 4 (CXCR4) was used as a reference biomarker.<h4>Methods</h4>A hybrid CXCR4 targeting peptide (MSAP-Ac-TZ14011) containing a fluorescent dye and a chelate for radioactive labeling was used to directly compare initial flow cytometry-based target validation in fresh tumor tissue to in vivo single photon emission computed tomography (SPECT) imaging and in vivo and ex vivo fluorescence imaging.<h4>Results</h4>Flow cytometric analysis of mouse tumor derived cell suspensions enabled discrimination between 4T1 control tumor lesions (with low levels of CXCR4 expression) and CXCR4 positive early, intermediate and late stage MIN-O lesions based on their CXCR4 expression levels; CXCR4(basal), CXCR4(+) and CXCR4(++) cell populations could be accurately discriminated. Mean fluorescent intensity ratios between expression in MIN-O and 4T1 tissue found with flow cytometry were comparable to ratios obtained with in vivo SPECT/CT and fluorescence imaging, ex vivo fluorescence evaluation and standard immunohistochemistry.<h4>Conclusion</h4>The hybrid nature of a targeting imaging agent like MSAP-Ac-TZ14011 enables integration of target selection, in vivo imaging and ex vivo validation using a single agent. The use of biopsy tissue for biomarker screening can readily be expanded to other targeting hybrid imaging agents and can possibly help increase the clinical applicability of tumor-specific imaging approaches.Tessa BuckleJoeri KuilNynke S van den BergAnton BunschotenHildo J LambHushan YuanLee JosephsonJos JonkersAlexander D BorowskyFijs W B van LeeuwenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e48324 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Tessa Buckle
Joeri Kuil
Nynke S van den Berg
Anton Bunschoten
Hildo J Lamb
Hushan Yuan
Lee Josephson
Jos Jonkers
Alexander D Borowsky
Fijs W B van Leeuwen
Use of a single hybrid imaging agent for integration of target validation with in vivo and ex vivo imaging of mouse tumor lesions resembling human DCIS.
description <h4>Unlabelled</h4>Screening of biomarker expression levels in tumor biopsy samples not only provides an assessment of prognostic and predictive factors, but may also be used for selection of biomarker-specific imaging strategies. To assess the feasibility of using a biopsy specimen for a personalized selection of an imaging agent, the chemokine receptor 4 (CXCR4) was used as a reference biomarker.<h4>Methods</h4>A hybrid CXCR4 targeting peptide (MSAP-Ac-TZ14011) containing a fluorescent dye and a chelate for radioactive labeling was used to directly compare initial flow cytometry-based target validation in fresh tumor tissue to in vivo single photon emission computed tomography (SPECT) imaging and in vivo and ex vivo fluorescence imaging.<h4>Results</h4>Flow cytometric analysis of mouse tumor derived cell suspensions enabled discrimination between 4T1 control tumor lesions (with low levels of CXCR4 expression) and CXCR4 positive early, intermediate and late stage MIN-O lesions based on their CXCR4 expression levels; CXCR4(basal), CXCR4(+) and CXCR4(++) cell populations could be accurately discriminated. Mean fluorescent intensity ratios between expression in MIN-O and 4T1 tissue found with flow cytometry were comparable to ratios obtained with in vivo SPECT/CT and fluorescence imaging, ex vivo fluorescence evaluation and standard immunohistochemistry.<h4>Conclusion</h4>The hybrid nature of a targeting imaging agent like MSAP-Ac-TZ14011 enables integration of target selection, in vivo imaging and ex vivo validation using a single agent. The use of biopsy tissue for biomarker screening can readily be expanded to other targeting hybrid imaging agents and can possibly help increase the clinical applicability of tumor-specific imaging approaches.
format article
author Tessa Buckle
Joeri Kuil
Nynke S van den Berg
Anton Bunschoten
Hildo J Lamb
Hushan Yuan
Lee Josephson
Jos Jonkers
Alexander D Borowsky
Fijs W B van Leeuwen
author_facet Tessa Buckle
Joeri Kuil
Nynke S van den Berg
Anton Bunschoten
Hildo J Lamb
Hushan Yuan
Lee Josephson
Jos Jonkers
Alexander D Borowsky
Fijs W B van Leeuwen
author_sort Tessa Buckle
title Use of a single hybrid imaging agent for integration of target validation with in vivo and ex vivo imaging of mouse tumor lesions resembling human DCIS.
title_short Use of a single hybrid imaging agent for integration of target validation with in vivo and ex vivo imaging of mouse tumor lesions resembling human DCIS.
title_full Use of a single hybrid imaging agent for integration of target validation with in vivo and ex vivo imaging of mouse tumor lesions resembling human DCIS.
title_fullStr Use of a single hybrid imaging agent for integration of target validation with in vivo and ex vivo imaging of mouse tumor lesions resembling human DCIS.
title_full_unstemmed Use of a single hybrid imaging agent for integration of target validation with in vivo and ex vivo imaging of mouse tumor lesions resembling human DCIS.
title_sort use of a single hybrid imaging agent for integration of target validation with in vivo and ex vivo imaging of mouse tumor lesions resembling human dcis.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/f6d330fe80da41a880a60b08992a5acf
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