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

Author(s)

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

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.

Organisation(s)

Department of Inorganic Chemistry, Joint Applied Medicinal Radiochemistry Facility

External organisation(s)

Medizinische Universität Wien, Paul Scherrer Institute, Research Cluster Translational Cancer Therapy Research, Ludwig Boltzmann Intitute Applied Diagnostics

Journal

Pharmaceutics

Volume

15

DOI

https://doi.org/10.3390/pharmaceutics15112626

Publication date

11-2023

Peer reviewed

Yes

Austrian Fields of Science 2012

301207 Pharmaceutical chemistry, 104003 Inorganic chemistry, 301904 Cancer research

Keywords

ASJC Scopus subject areas

Pharmaceutical Science

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Portal url

https://ucrisportal.univie.ac.at/en/publications/b74ad17e-23f8-4366-842e-8af8a11f8ad5