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Synthesis and Preclinical Evaluation of Radiolabeled [(103)Ru]BOLD-100

The first-in-class ruthenium-based chemotherapeutic agent BOLD-100 (formerly IT-139, NKP-1339, KP1339) is currently the subject of clinical evaluation for the treatment of gastric, pancreatic, colorectal and bile duct cancer. A radiolabeled version of the compound could present a helpful diagnostic...

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Autores principales: Happl, Barbara, Brandt, Marie, Balber, Theresa, Benčurová, Katarína, Talip, Zeynep, Voegele, Alexander, Heffeter, Petra, Kandioller, Wolfgang, Van der Meulen, Nicholas P., Mitterhauser, Markus, Hacker, Marcus, Keppler, Bernhard K., Mindt, Thomas L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10674160/
https://www.ncbi.nlm.nih.gov/pubmed/38004604
http://dx.doi.org/10.3390/pharmaceutics15112626
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author Happl, Barbara
Brandt, Marie
Balber, Theresa
Benčurová, Katarína
Talip, Zeynep
Voegele, Alexander
Heffeter, Petra
Kandioller, Wolfgang
Van der Meulen, Nicholas P.
Mitterhauser, Markus
Hacker, Marcus
Keppler, Bernhard K.
Mindt, Thomas L.
author_facet Happl, Barbara
Brandt, Marie
Balber, Theresa
Benčurová, Katarína
Talip, Zeynep
Voegele, Alexander
Heffeter, Petra
Kandioller, Wolfgang
Van der Meulen, Nicholas P.
Mitterhauser, Markus
Hacker, Marcus
Keppler, Bernhard K.
Mindt, Thomas L.
author_sort Happl, Barbara
collection PubMed
description The first-in-class ruthenium-based chemotherapeutic agent BOLD-100 (formerly IT-139, NKP-1339, KP1339) is currently the subject of clinical evaluation for the treatment of gastric, pancreatic, colorectal and bile duct cancer. A radiolabeled version of the compound could present a helpful diagnostic tool. Thus, this study investigated the pharmacokinetics of BOLD-100 in more detail to facilitate the stratification of patients for the therapy. The synthesis of [(103)Ru]BOLD-100, radiolabeled with carrier added (c.a.) ruthenium-103, was established and the product was characterized by HPLC and UV/Vis spectroscopy. In order to compare the radiolabeled and non-radioactive versions of BOLD-100, both complexes were fully evaluated in vitro and in vivo. The cytotoxicity of the compounds was determined in two colon carcinoma cell lines (HCT116 and CT26) and biodistribution studies were performed in Balb/c mice bearing CT26 allografts over a time period of 72 h post injection (p.i.). We report herein preclinical cytotoxicity and pharmacokinetic data for BOLD-100, which were found to be identical to those of its radiolabeled analog [(103)Ru]BOLD-100.
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spelling pubmed-106741602023-11-15 Synthesis and Preclinical Evaluation of Radiolabeled [(103)Ru]BOLD-100 Happl, Barbara Brandt, Marie Balber, Theresa Benčurová, Katarína Talip, Zeynep Voegele, Alexander Heffeter, Petra Kandioller, Wolfgang Van der Meulen, Nicholas P. Mitterhauser, Markus Hacker, Marcus Keppler, Bernhard K. Mindt, Thomas L. Pharmaceutics Article The first-in-class ruthenium-based chemotherapeutic agent BOLD-100 (formerly IT-139, NKP-1339, KP1339) is currently the subject of clinical evaluation for the treatment of gastric, pancreatic, colorectal and bile duct cancer. A radiolabeled version of the compound could present a helpful diagnostic tool. Thus, this study investigated the pharmacokinetics of BOLD-100 in more detail to facilitate the stratification of patients for the therapy. The synthesis of [(103)Ru]BOLD-100, radiolabeled with carrier added (c.a.) ruthenium-103, was established and the product was characterized by HPLC and UV/Vis spectroscopy. In order to compare the radiolabeled and non-radioactive versions of BOLD-100, both complexes were fully evaluated in vitro and in vivo. The cytotoxicity of the compounds was determined in two colon carcinoma cell lines (HCT116 and CT26) and biodistribution studies were performed in Balb/c mice bearing CT26 allografts over a time period of 72 h post injection (p.i.). We report herein preclinical cytotoxicity and pharmacokinetic data for BOLD-100, which were found to be identical to those of its radiolabeled analog [(103)Ru]BOLD-100. MDPI 2023-11-15 /pmc/articles/PMC10674160/ /pubmed/38004604 http://dx.doi.org/10.3390/pharmaceutics15112626 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Happl, Barbara
Brandt, Marie
Balber, Theresa
Benčurová, Katarína
Talip, Zeynep
Voegele, Alexander
Heffeter, Petra
Kandioller, Wolfgang
Van der Meulen, Nicholas P.
Mitterhauser, Markus
Hacker, Marcus
Keppler, Bernhard K.
Mindt, Thomas L.
Synthesis and Preclinical Evaluation of Radiolabeled [(103)Ru]BOLD-100
title Synthesis and Preclinical Evaluation of Radiolabeled [(103)Ru]BOLD-100
title_full Synthesis and Preclinical Evaluation of Radiolabeled [(103)Ru]BOLD-100
title_fullStr Synthesis and Preclinical Evaluation of Radiolabeled [(103)Ru]BOLD-100
title_full_unstemmed Synthesis and Preclinical Evaluation of Radiolabeled [(103)Ru]BOLD-100
title_short Synthesis and Preclinical Evaluation of Radiolabeled [(103)Ru]BOLD-100
title_sort synthesis and preclinical evaluation of radiolabeled [(103)ru]bold-100
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10674160/
https://www.ncbi.nlm.nih.gov/pubmed/38004604
http://dx.doi.org/10.3390/pharmaceutics15112626
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