Synthesis and preclinical evaluation of BOLD-100 radiolabeled with ruthenium-97 and ruthenium-103

Author(s): B. Happl, T. Balber, P. Heffeter, C. Denk, J. M. Welch, U. Köster, C. Alliot, A. C. Bonraisin, M. Brandt, F. Haddad, J. H. Sterba, W. Kandioller, M. Mitterhauser, M. Hacker, B. K. Keppler, T. L. Mindt
Abstract: BOLD-100 (formerly IT-139, KP1339), a well-established chemotherapeutic agent, is currently being investigated in clinical trials for the treatment of gastric, pancreatic, colorectal, and bile duct cancer. Despite numerous studies, the exact mode of action is still the subject of discussions. Radiolabeled BOLD-100 could be a powerful tool to clarify pharmacokinetic pathways of the compound and to predict therapy responses in patients using nuclear molecular imaging prior to the therapy. In this study, the radiosyntheses of carrier-added (c.a.) [^97/103Ru]BOLD-100 were performed with the two ruthenium isotopes ruthenium-103 (¹⁰³Ru; β⁻, γ) and ruthenium-97 (⁹⁷Ru; EC, γ), of which in particular the latter isotope is suitable for imaging by single-photon emission computed tomography (SPECT). To identify the best tumor-to-background ratio for diagnostic imaging, biodistribution studies were performed with two different injected doses of c.a. [¹⁰³Ru]BOLD-100 (3 and 30 mg kg⁻¹) in Balb/c mice bearing CT26 allografts over a time period of 72 h. Additionally, ex vivo autoradiography of the tumors (24 h p.i.) was conducted. Our results indicate that the higher injected dose (30 mg kg⁻¹) leads to more unspecific accumulation of the compound in non-targeted tissue, which is likely due to an overload of the albumin transport system. It was also shown that lower amounts of injected c.a. [¹⁰³Ru]BOLD-100 resulted in a relatively higher tumor uptake and, therefore, a better tumor-to-background ratio, which are encouraging results for future imaging studies using c.a. [⁹⁷Ru]BOLD-100.
Organisation(s): Department of Inorganic Chemistry, Joint Applied Medicinal Radiochemistry Facility
External organisation(s): Medizinische Universität Wien, Research Cluster Translational Cancer Therapy Research, Technische Universität Wien, Institut Laue-Langevin (ILL), GIP ARRONAX, Université de Nantes
Journal: Dalton Transactions
ISSN: 1477-9226
DOI: https://doi.org/10.1039/d4dt00118d
Publication date: 2024
Peer reviewed: Yes
Austrian Fields of Science 2012: 104003 Inorganic chemistry, 104020 Radiochemistry, 301904 Cancer research
ASJC Scopus subject areas: Inorganic Chemistry
Sustainable Development Goals: SDG 3 - Good Health and Well-being
Portal url: https://ucrisportal.univie.ac.at/en/publications/c32570cc-643b-4e35-88d6-d2c8313e6795