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Affibody-DyLight Conjugates for In Vivo Assessment of HER2 Expression by Near-Infrared Optical Imaging

PURPOSE: Amplification of the HER2/neu gene and/or overexpression of the corresponding protein have been identified in approximately 20% of invasive breast carcinomas. Assessment of HER2 expression in vivo would advance development of new HER2-targeted therapeutic agents and, potentially, facilitate...

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Autores principales: Zielinski, Rafal, Hassan, Moinuddin, Lyakhov, Ilya, Needle, Danielle, Chernomordik, Victor, Garcia-Glaessner, Alejandra, Ardeshirpour, Yasaman, Capala, Jacek, Gandjbakhche, Amir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401287/
https://www.ncbi.nlm.nih.gov/pubmed/22911732
http://dx.doi.org/10.1371/journal.pone.0041016
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author Zielinski, Rafal
Hassan, Moinuddin
Lyakhov, Ilya
Needle, Danielle
Chernomordik, Victor
Garcia-Glaessner, Alejandra
Ardeshirpour, Yasaman
Capala, Jacek
Gandjbakhche, Amir
author_facet Zielinski, Rafal
Hassan, Moinuddin
Lyakhov, Ilya
Needle, Danielle
Chernomordik, Victor
Garcia-Glaessner, Alejandra
Ardeshirpour, Yasaman
Capala, Jacek
Gandjbakhche, Amir
author_sort Zielinski, Rafal
collection PubMed
description PURPOSE: Amplification of the HER2/neu gene and/or overexpression of the corresponding protein have been identified in approximately 20% of invasive breast carcinomas. Assessment of HER2 expression in vivo would advance development of new HER2-targeted therapeutic agents and, potentially, facilitate choice of the proper treatment strategy offered to the individual patient. We present novel HER2-specific probes for in vivo evaluation of the receptor status by near-infrared (NIR) optical imaging. EXPERIMENTAL DESIGN: Affibody molecules were expressed, purified, and labeled with NIR-fluorescent dyes. The binding affinity and specificity of the obtained probe were tested in vitro. For in vivo validation, the relationship of the measured NIR signal and HER2 expression was characterized in four breast cancer xenograft models, expressing different levels of HER2. Accumulation of Affibody molecules in tumor tissue was further confirmed by ex vivo analysis. RESULTS: Affibody-DyLight conjugates showed high affinity to HER2 (K(D) = 3.66±0.26). No acute toxicity resulted from injection of the probes (up to 0.5 mg/kg) into mice. Pharmacokinetic studies revealed a relatively short (37.53±2.8 min) half-life of the tracer in blood. Fluorescence accumulation in HER2-positive BT-474 xenografts was evident as soon as a few minutes post injection and reached its maximum at 90 minutes. On the other hand, no signal retention was observed in HER2-negative MDA-MB-468 xenografts. Immunostaining of extracted tumor tissue confirmed penetration of the tracer into tumor tissue. CONCLUSIONS: The results of our studies suggest that Affibody-DyLight-750 conjugate is a powerful tool to monitor HER2 status in a preclinical setting. Following clinical validation, it might provide complementary means for assessment of HER2 expression in breast cancer patients (assuming availability of proper NIR scanners) and/or be used to facilitate detection of HER2-positive metastatic lesions during NIR-assisted surgery.
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spelling pubmed-34012872012-07-30 Affibody-DyLight Conjugates for In Vivo Assessment of HER2 Expression by Near-Infrared Optical Imaging Zielinski, Rafal Hassan, Moinuddin Lyakhov, Ilya Needle, Danielle Chernomordik, Victor Garcia-Glaessner, Alejandra Ardeshirpour, Yasaman Capala, Jacek Gandjbakhche, Amir PLoS One Research Article PURPOSE: Amplification of the HER2/neu gene and/or overexpression of the corresponding protein have been identified in approximately 20% of invasive breast carcinomas. Assessment of HER2 expression in vivo would advance development of new HER2-targeted therapeutic agents and, potentially, facilitate choice of the proper treatment strategy offered to the individual patient. We present novel HER2-specific probes for in vivo evaluation of the receptor status by near-infrared (NIR) optical imaging. EXPERIMENTAL DESIGN: Affibody molecules were expressed, purified, and labeled with NIR-fluorescent dyes. The binding affinity and specificity of the obtained probe were tested in vitro. For in vivo validation, the relationship of the measured NIR signal and HER2 expression was characterized in four breast cancer xenograft models, expressing different levels of HER2. Accumulation of Affibody molecules in tumor tissue was further confirmed by ex vivo analysis. RESULTS: Affibody-DyLight conjugates showed high affinity to HER2 (K(D) = 3.66±0.26). No acute toxicity resulted from injection of the probes (up to 0.5 mg/kg) into mice. Pharmacokinetic studies revealed a relatively short (37.53±2.8 min) half-life of the tracer in blood. Fluorescence accumulation in HER2-positive BT-474 xenografts was evident as soon as a few minutes post injection and reached its maximum at 90 minutes. On the other hand, no signal retention was observed in HER2-negative MDA-MB-468 xenografts. Immunostaining of extracted tumor tissue confirmed penetration of the tracer into tumor tissue. CONCLUSIONS: The results of our studies suggest that Affibody-DyLight-750 conjugate is a powerful tool to monitor HER2 status in a preclinical setting. Following clinical validation, it might provide complementary means for assessment of HER2 expression in breast cancer patients (assuming availability of proper NIR scanners) and/or be used to facilitate detection of HER2-positive metastatic lesions during NIR-assisted surgery. Public Library of Science 2012-07-20 /pmc/articles/PMC3401287/ /pubmed/22911732 http://dx.doi.org/10.1371/journal.pone.0041016 Text en This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Zielinski, Rafal
Hassan, Moinuddin
Lyakhov, Ilya
Needle, Danielle
Chernomordik, Victor
Garcia-Glaessner, Alejandra
Ardeshirpour, Yasaman
Capala, Jacek
Gandjbakhche, Amir
Affibody-DyLight Conjugates for In Vivo Assessment of HER2 Expression by Near-Infrared Optical Imaging
title Affibody-DyLight Conjugates for In Vivo Assessment of HER2 Expression by Near-Infrared Optical Imaging
title_full Affibody-DyLight Conjugates for In Vivo Assessment of HER2 Expression by Near-Infrared Optical Imaging
title_fullStr Affibody-DyLight Conjugates for In Vivo Assessment of HER2 Expression by Near-Infrared Optical Imaging
title_full_unstemmed Affibody-DyLight Conjugates for In Vivo Assessment of HER2 Expression by Near-Infrared Optical Imaging
title_short Affibody-DyLight Conjugates for In Vivo Assessment of HER2 Expression by Near-Infrared Optical Imaging
title_sort affibody-dylight conjugates for in vivo assessment of her2 expression by near-infrared optical imaging
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401287/
https://www.ncbi.nlm.nih.gov/pubmed/22911732
http://dx.doi.org/10.1371/journal.pone.0041016
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