Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Wurzer, Alexander, Seidl, Christof, Morgenstern, Alfred, Bruchertseifer, Frank, Schwaiger, Markus, Wester, Hans‐Jürgen, Notni, Johannes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
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
_version_ 1783300152762564608
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
work_keys_str_mv AT wurzeralexander dualnuclideradiopharmaceuticalsforpositronemissiontomographybaseddosimetryinradiotherapy
AT seidlchristof dualnuclideradiopharmaceuticalsforpositronemissiontomographybaseddosimetryinradiotherapy
AT morgensternalfred dualnuclideradiopharmaceuticalsforpositronemissiontomographybaseddosimetryinradiotherapy
AT bruchertseiferfrank dualnuclideradiopharmaceuticalsforpositronemissiontomographybaseddosimetryinradiotherapy
AT schwaigermarkus dualnuclideradiopharmaceuticalsforpositronemissiontomographybaseddosimetryinradiotherapy
AT westerhansjurgen dualnuclideradiopharmaceuticalsforpositronemissiontomographybaseddosimetryinradiotherapy
AT notnijohannes dualnuclideradiopharmaceuticalsforpositronemissiontomographybaseddosimetryinradiotherapy