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Synthesis of a novel (89)Zr-labeled HER2 affibody and its application study in tumor PET imaging
BACKGROUND: Human epidermal growth factor receptor-2 (HER2) is an essential biomarker for tumor treatment. Affibody is an ideal vector for preparing HER2 specific probes because of high affinity and rapid clearance from normal tissues, etc. Zirconium-89 is a PET imaging isotope with a long half-life...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271293/ https://www.ncbi.nlm.nih.gov/pubmed/32495181 http://dx.doi.org/10.1186/s13550-020-00649-7 |
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author | Xu, Yuping Wang, Lizhen Pan, Donghui Yan, Junjie Wang, Xinyu Yang, Runlin Li, Mingzhu Liu, Yu Yang, Min |
author_facet | Xu, Yuping Wang, Lizhen Pan, Donghui Yan, Junjie Wang, Xinyu Yang, Runlin Li, Mingzhu Liu, Yu Yang, Min |
author_sort | Xu, Yuping |
collection | PubMed |
description | BACKGROUND: Human epidermal growth factor receptor-2 (HER2) is an essential biomarker for tumor treatment. Affibody is an ideal vector for preparing HER2 specific probes because of high affinity and rapid clearance from normal tissues, etc. Zirconium-89 is a PET imaging isotope with a long half-life and suitable for monitoring biological processes for more extended periods. In this study, a novel (89)Zr-labeled HER2 affibody, [(89)Zr]Zr-DFO-MAL-Cys-MZHER2, was synthesized, and its imaging characters were also assessed. RESULTS: The precursor, DFO-MAL-Cys-MZHER2, was obtained with a yield of nearly 50%. The radiochemical yield of [(89)Zr]Zr -DFO-MAL-Cys-MZHER2 was 90.2 ± 1.9%, and the radiochemical purity was higher than 95%. The total synthesis time was only 30 min. The probe was stable in PBS and serum. The tracer accumulated in HER2 overexpressing human ovarian cancer SKOV-3 cells. In vivo studies in mice bearing tumors showed that the probe was highly retained in SKOV-3 xenografts even for 48 h. The tumors were visualized with good contrast to normal tissues. ROI analysis revealed that the average uptake values in the tumor were greater than 5% IA/g during 48 h postinjection. On the contrary, the counterparts of MCF-7 tumors kept low levels ( ~ 1% IA/g). The outcome was consistent with the immunohistochemical analysis and ex vivo autoradiography. The probe quickly cleared from the normal organs except kidneys and mainly excreted through the urinary system. CONCLUSION: The novel HER2 affibody for PET imaging was easily prepared with satisfactory labeling yield and radiochemical purity. [(89)Zr]Zr-DFO-MAL-Cys-MZHER2 is a potential candidate for detecting HER2 expression. It may play specific roles in clinical cancer theranostics. |
format | Online Article Text |
id | pubmed-7271293 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-72712932020-06-15 Synthesis of a novel (89)Zr-labeled HER2 affibody and its application study in tumor PET imaging Xu, Yuping Wang, Lizhen Pan, Donghui Yan, Junjie Wang, Xinyu Yang, Runlin Li, Mingzhu Liu, Yu Yang, Min EJNMMI Res Original Research BACKGROUND: Human epidermal growth factor receptor-2 (HER2) is an essential biomarker for tumor treatment. Affibody is an ideal vector for preparing HER2 specific probes because of high affinity and rapid clearance from normal tissues, etc. Zirconium-89 is a PET imaging isotope with a long half-life and suitable for monitoring biological processes for more extended periods. In this study, a novel (89)Zr-labeled HER2 affibody, [(89)Zr]Zr-DFO-MAL-Cys-MZHER2, was synthesized, and its imaging characters were also assessed. RESULTS: The precursor, DFO-MAL-Cys-MZHER2, was obtained with a yield of nearly 50%. The radiochemical yield of [(89)Zr]Zr -DFO-MAL-Cys-MZHER2 was 90.2 ± 1.9%, and the radiochemical purity was higher than 95%. The total synthesis time was only 30 min. The probe was stable in PBS and serum. The tracer accumulated in HER2 overexpressing human ovarian cancer SKOV-3 cells. In vivo studies in mice bearing tumors showed that the probe was highly retained in SKOV-3 xenografts even for 48 h. The tumors were visualized with good contrast to normal tissues. ROI analysis revealed that the average uptake values in the tumor were greater than 5% IA/g during 48 h postinjection. On the contrary, the counterparts of MCF-7 tumors kept low levels ( ~ 1% IA/g). The outcome was consistent with the immunohistochemical analysis and ex vivo autoradiography. The probe quickly cleared from the normal organs except kidneys and mainly excreted through the urinary system. CONCLUSION: The novel HER2 affibody for PET imaging was easily prepared with satisfactory labeling yield and radiochemical purity. [(89)Zr]Zr-DFO-MAL-Cys-MZHER2 is a potential candidate for detecting HER2 expression. It may play specific roles in clinical cancer theranostics. Springer Berlin Heidelberg 2020-06-03 /pmc/articles/PMC7271293/ /pubmed/32495181 http://dx.doi.org/10.1186/s13550-020-00649-7 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Original Research Xu, Yuping Wang, Lizhen Pan, Donghui Yan, Junjie Wang, Xinyu Yang, Runlin Li, Mingzhu Liu, Yu Yang, Min Synthesis of a novel (89)Zr-labeled HER2 affibody and its application study in tumor PET imaging |
title | Synthesis of a novel (89)Zr-labeled HER2 affibody and its application study in tumor PET imaging |
title_full | Synthesis of a novel (89)Zr-labeled HER2 affibody and its application study in tumor PET imaging |
title_fullStr | Synthesis of a novel (89)Zr-labeled HER2 affibody and its application study in tumor PET imaging |
title_full_unstemmed | Synthesis of a novel (89)Zr-labeled HER2 affibody and its application study in tumor PET imaging |
title_short | Synthesis of a novel (89)Zr-labeled HER2 affibody and its application study in tumor PET imaging |
title_sort | synthesis of a novel (89)zr-labeled her2 affibody and its application study in tumor pet imaging |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271293/ https://www.ncbi.nlm.nih.gov/pubmed/32495181 http://dx.doi.org/10.1186/s13550-020-00649-7 |
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