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

Barbara Happl; Marie Brandt; Theresa Balber; Katarína Benčurová; Zeynep Talip; Alexander Voegele; Petra Heffeter; Wolfgang Kandioller; Nicholas P. Van der Meulen; Markus Mitterhauser; Marcus Hacker; Bernhard K. Keppler; Thomas L. Mindt

doi:10.3390/pharmaceutics15112626

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

Barbara Happl, Marie Brandt, Theresa Balber, Katarína Benčurová, Zeynep Talip, Alexander Voegele, Petra Heffeter, Wolfgang Kandioller, Nicholas P. Van der Meulen, Markus Mitterhauser (Corresponding author), Marcus Hacker, Bernhard K. Keppler, Thomas L. Mindt (Corresponding author)

Publications: Contribution to journal › Article › Peer Reviewed

Abstract

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 [¹⁰³Ru]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 [¹⁰³Ru]BOLD-100.

Original language	English
Article number	2626
Journal	Pharmaceutics
Volume	15
Issue number	11
DOIs	https://doi.org/10.3390/pharmaceutics15112626
Publication status	Published - Nov 2023

Austrian Fields of Science 2012

301207 Pharmaceutical chemistry
104003 Inorganic chemistry
301904 Cancer research

Keywords

anti-cancer metallodrugs
BOLD-100
in vivo studies
pharmacokinetics
ruthenium-103

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.3390/pharmaceutics15112626Licence: CC BY 4.0

https://phaidra.univie.ac.at/o:2045439Licence: CC BY 4.0

Cite this

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title = "Synthesis and Preclinical Evaluation of Radiolabeled [103Ru]BOLD-100",

abstract = "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 [103Ru]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 [103Ru]BOLD-100.",

keywords = "anti-cancer metallodrugs, BOLD-100, in vivo studies, pharmacokinetics, ruthenium-103",

author = "Barbara Happl and Marie Brandt and Theresa Balber and Katar{\'i}na Ben{\v c}urov{\'a} and Zeynep Talip and Alexander Voegele and Petra Heffeter and Wolfgang Kandioller and {Van der Meulen}, {Nicholas P.} and Markus Mitterhauser and Marcus Hacker and Keppler, {Bernhard K.} and Mindt, {Thomas L.}",

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doi = "10.3390/pharmaceutics15112626",

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T1 - Synthesis and Preclinical Evaluation of Radiolabeled [103Ru]BOLD-100

AU - Happl, Barbara

AU - Brandt, Marie

AU - Balber, Theresa

AU - Benčurová, Katarína

AU - Talip, Zeynep

AU - Voegele, Alexander

AU - Heffeter, Petra

AU - Kandioller, Wolfgang

AU - Van der Meulen, Nicholas P.

AU - Mitterhauser, Markus

AU - Hacker, Marcus

AU - Keppler, Bernhard K.

AU - Mindt, Thomas L.

N1 - Accession Number: WOS:001114517300001 PubMed ID: 38004604

PY - 2023/11

Y1 - 2023/11

N2 - 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 [103Ru]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 [103Ru]BOLD-100.

AB - 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 [103Ru]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 [103Ru]BOLD-100.

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