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Novel Bifunctional Cyclic Chelator for (89)Zr Labeling–Radiolabeling and Targeting Properties of RGD Conjugates
[Image: see text] Within the last years (89)Zr has attracted considerable attention as long-lived radionuclide for positron emission tomography (PET) applications. So far desferrioxamine B (DFO) has been mainly used as bifunctional chelating system. Fusarinine C (FSC), having complexing properties c...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2015
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453016/ https://www.ncbi.nlm.nih.gov/pubmed/25941834 http://dx.doi.org/10.1021/acs.molpharmaceut.5b00128 |
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author | Zhai, Chuangyan Summer, Dominik Rangger, Christine Franssen, Gerben M. Laverman, Peter Haas, Hubertus Petrik, Milos Haubner, Roland Decristoforo, Clemens |
author_facet | Zhai, Chuangyan Summer, Dominik Rangger, Christine Franssen, Gerben M. Laverman, Peter Haas, Hubertus Petrik, Milos Haubner, Roland Decristoforo, Clemens |
author_sort | Zhai, Chuangyan |
collection | PubMed |
description | [Image: see text] Within the last years (89)Zr has attracted considerable attention as long-lived radionuclide for positron emission tomography (PET) applications. So far desferrioxamine B (DFO) has been mainly used as bifunctional chelating system. Fusarinine C (FSC), having complexing properties comparable to DFO, was expected to be an alternative with potentially higher stability due to its cyclic structure. In this study, as proof of principle, various FSC-RGD conjugates targeting α(v)ß(3) integrins were synthesized using different conjugation strategies and labeled with (89)Zr. In vitro stability, biodistribution, and microPET/CT imaging were evaluated using [(89)Zr]FSC-RGD conjugates or [(89)Zr]triacetylfusarinine C (TAFC). Quantitative (89)Zr labeling was achieved within 90 min at room temperature. The distribution coefficients of the different radioligands indicate hydrophilic character. Compared to [(89)Zr]DFO, [(89)Zr]FSC derivatives showed excellent in vitro stability and resistance against transchelation in phosphate buffered saline (PBS), ethylenediaminetetraacetic acid solution (EDTA), and human serum for up to 7 days. Cell binding studies and biodistribution as well as microPET/CT imaging experiments showed efficient receptor-specific targeting of [(89)Zr]FSC-RGD conjugates. No bone uptake was observed analyzing PET images indicating high in vivo stability. These findings indicate that FSC is a highly promising chelator for the development of (89)Zr-based PET imaging agents. |
format | Online Article Text |
id | pubmed-4453016 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-44530162015-06-04 Novel Bifunctional Cyclic Chelator for (89)Zr Labeling–Radiolabeling and Targeting Properties of RGD Conjugates Zhai, Chuangyan Summer, Dominik Rangger, Christine Franssen, Gerben M. Laverman, Peter Haas, Hubertus Petrik, Milos Haubner, Roland Decristoforo, Clemens Mol Pharm [Image: see text] Within the last years (89)Zr has attracted considerable attention as long-lived radionuclide for positron emission tomography (PET) applications. So far desferrioxamine B (DFO) has been mainly used as bifunctional chelating system. Fusarinine C (FSC), having complexing properties comparable to DFO, was expected to be an alternative with potentially higher stability due to its cyclic structure. In this study, as proof of principle, various FSC-RGD conjugates targeting α(v)ß(3) integrins were synthesized using different conjugation strategies and labeled with (89)Zr. In vitro stability, biodistribution, and microPET/CT imaging were evaluated using [(89)Zr]FSC-RGD conjugates or [(89)Zr]triacetylfusarinine C (TAFC). Quantitative (89)Zr labeling was achieved within 90 min at room temperature. The distribution coefficients of the different radioligands indicate hydrophilic character. Compared to [(89)Zr]DFO, [(89)Zr]FSC derivatives showed excellent in vitro stability and resistance against transchelation in phosphate buffered saline (PBS), ethylenediaminetetraacetic acid solution (EDTA), and human serum for up to 7 days. Cell binding studies and biodistribution as well as microPET/CT imaging experiments showed efficient receptor-specific targeting of [(89)Zr]FSC-RGD conjugates. No bone uptake was observed analyzing PET images indicating high in vivo stability. These findings indicate that FSC is a highly promising chelator for the development of (89)Zr-based PET imaging agents. American Chemical Society 2015-05-05 2015-06-01 /pmc/articles/PMC4453016/ /pubmed/25941834 http://dx.doi.org/10.1021/acs.molpharmaceut.5b00128 Text en Copyright © 2015 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. |
spellingShingle | Zhai, Chuangyan Summer, Dominik Rangger, Christine Franssen, Gerben M. Laverman, Peter Haas, Hubertus Petrik, Milos Haubner, Roland Decristoforo, Clemens Novel Bifunctional Cyclic Chelator for (89)Zr Labeling–Radiolabeling and Targeting Properties of RGD Conjugates |
title | Novel Bifunctional Cyclic Chelator for (89)Zr Labeling–Radiolabeling and Targeting Properties of RGD
Conjugates |
title_full | Novel Bifunctional Cyclic Chelator for (89)Zr Labeling–Radiolabeling and Targeting Properties of RGD
Conjugates |
title_fullStr | Novel Bifunctional Cyclic Chelator for (89)Zr Labeling–Radiolabeling and Targeting Properties of RGD
Conjugates |
title_full_unstemmed | Novel Bifunctional Cyclic Chelator for (89)Zr Labeling–Radiolabeling and Targeting Properties of RGD
Conjugates |
title_short | Novel Bifunctional Cyclic Chelator for (89)Zr Labeling–Radiolabeling and Targeting Properties of RGD
Conjugates |
title_sort | novel bifunctional cyclic chelator for (89)zr labeling–radiolabeling and targeting properties of rgd
conjugates |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453016/ https://www.ncbi.nlm.nih.gov/pubmed/25941834 http://dx.doi.org/10.1021/acs.molpharmaceut.5b00128 |
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