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Dual‐Nuclide Radiopharmaceuticals for Positron Emission Tomography Based Dosimetry in Radiotherapy
Improvement of the accuracy of dosimetry in radionuclide therapy has the potential to increase patient safety and therapeutic outcomes. Although positron emission tomography (PET) is ideally suited for acquisition of dosimetric data because PET is inherently quantitative and offers high sensitivity...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813229/ https://www.ncbi.nlm.nih.gov/pubmed/28833667 http://dx.doi.org/10.1002/chem.201702335 |
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author | Wurzer, Alexander Seidl, Christof Morgenstern, Alfred Bruchertseifer, Frank Schwaiger, Markus Wester, Hans‐Jürgen Notni, Johannes |
author_facet | Wurzer, Alexander Seidl, Christof Morgenstern, Alfred Bruchertseifer, Frank Schwaiger, Markus Wester, Hans‐Jürgen Notni, Johannes |
author_sort | Wurzer, Alexander |
collection | PubMed |
description | Improvement of the accuracy of dosimetry in radionuclide therapy has the potential to increase patient safety and therapeutic outcomes. Although positron emission tomography (PET) is ideally suited for acquisition of dosimetric data because PET is inherently quantitative and offers high sensitivity and spatial resolution, it is not directly applicable for this purpose because common therapeutic radionuclides lack the necessary positron emission. This work reports on the synthesis of dual‐nuclide labeled radiopharmaceuticals with therapeutic and PET functionality, which are based on common and widely available metal radionuclides. Dual‐chelator conjugates, featuring interlinked cyclen‐ and triazacyclononane‐based polyphosphinates DOTPI and TRAP, allow for strictly regioselective complexation of therapeutic (e.g., (177)Lu, (90)Y, or (213)Bi) and PET (e.g., (68)Ga) radiometals in the same molecular framework by exploiting the orthogonal metal ion selectivity of these chelators (DOTPI: large cations, such as lanthanide(III) ions; TRAP: small trivalent ions, such as Ga(III)). Such DOTPI–TRAP conjugates were decorated with 3 Gly‐urea‐Lys (KuE) motifs for targeting prostate‐specific membrane antigen (PSMA), employing Cu‐catalyzed (CuAAC) as well as strain‐promoted (SPAAC) click chemistry. These were labeled with (177)Lu or (213)Bi and (68)Ga and used for in vivo imaging of LNCaP (human prostate carcinoma) tumor xenografts in SCID mice by PET, thus proving practical applicability of the concept. |
format | Online Article Text |
id | pubmed-5813229 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-58132292018-02-21 Dual‐Nuclide Radiopharmaceuticals for Positron Emission Tomography Based Dosimetry in Radiotherapy Wurzer, Alexander Seidl, Christof Morgenstern, Alfred Bruchertseifer, Frank Schwaiger, Markus Wester, Hans‐Jürgen Notni, Johannes Chemistry Communications Improvement of the accuracy of dosimetry in radionuclide therapy has the potential to increase patient safety and therapeutic outcomes. Although positron emission tomography (PET) is ideally suited for acquisition of dosimetric data because PET is inherently quantitative and offers high sensitivity and spatial resolution, it is not directly applicable for this purpose because common therapeutic radionuclides lack the necessary positron emission. This work reports on the synthesis of dual‐nuclide labeled radiopharmaceuticals with therapeutic and PET functionality, which are based on common and widely available metal radionuclides. Dual‐chelator conjugates, featuring interlinked cyclen‐ and triazacyclononane‐based polyphosphinates DOTPI and TRAP, allow for strictly regioselective complexation of therapeutic (e.g., (177)Lu, (90)Y, or (213)Bi) and PET (e.g., (68)Ga) radiometals in the same molecular framework by exploiting the orthogonal metal ion selectivity of these chelators (DOTPI: large cations, such as lanthanide(III) ions; TRAP: small trivalent ions, such as Ga(III)). Such DOTPI–TRAP conjugates were decorated with 3 Gly‐urea‐Lys (KuE) motifs for targeting prostate‐specific membrane antigen (PSMA), employing Cu‐catalyzed (CuAAC) as well as strain‐promoted (SPAAC) click chemistry. These were labeled with (177)Lu or (213)Bi and (68)Ga and used for in vivo imaging of LNCaP (human prostate carcinoma) tumor xenografts in SCID mice by PET, thus proving practical applicability of the concept. John Wiley and Sons Inc. 2017-09-14 2018-01-12 /pmc/articles/PMC5813229/ /pubmed/28833667 http://dx.doi.org/10.1002/chem.201702335 Text en © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Communications Wurzer, Alexander Seidl, Christof Morgenstern, Alfred Bruchertseifer, Frank Schwaiger, Markus Wester, Hans‐Jürgen Notni, Johannes Dual‐Nuclide Radiopharmaceuticals for Positron Emission Tomography Based Dosimetry in Radiotherapy |
title | Dual‐Nuclide Radiopharmaceuticals for Positron Emission Tomography Based Dosimetry in Radiotherapy |
title_full | Dual‐Nuclide Radiopharmaceuticals for Positron Emission Tomography Based Dosimetry in Radiotherapy |
title_fullStr | Dual‐Nuclide Radiopharmaceuticals for Positron Emission Tomography Based Dosimetry in Radiotherapy |
title_full_unstemmed | Dual‐Nuclide Radiopharmaceuticals for Positron Emission Tomography Based Dosimetry in Radiotherapy |
title_short | Dual‐Nuclide Radiopharmaceuticals for Positron Emission Tomography Based Dosimetry in Radiotherapy |
title_sort | dual‐nuclide radiopharmaceuticals for positron emission tomography based dosimetry in radiotherapy |
topic | Communications |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813229/ https://www.ncbi.nlm.nih.gov/pubmed/28833667 http://dx.doi.org/10.1002/chem.201702335 |
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