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

Pharmaceutics. 2023 Nov 15;15(11):2626. doi: 10.3390/pharmaceutics15112626.

Authors

Barbara Happl^{1

2

3}, Marie Brandt^{1

2

4}, Theresa Balber^{1

2

4}, Katarína Benčurová^{1

2}, Zeynep Talip⁵, Alexander Voegele⁶, Petra Heffeter^{7

8}, Wolfgang Kandioller^{3

8}, Nicholas P Van der Meulen^{5

6}, Markus Mitterhauser^{1

2

3

4}, Marcus Hacker², Bernhard K Keppler^{3

8}, Thomas L Mindt^{1

2

3

4}

Affiliations

¹ Ludwig Boltzmann Institute Applied Diagnostics, General Hospital of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
² Division of Nuclear Medicine, Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
³ Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Strasse 42, 1090 Vienna, Austria.
⁴ Joint Applied Medicinal Radiochemistry Facility, University of Vienna, Medical University of Vienna, 1090 Vienna, Austria.
⁵ Center for Radiopharmaceutical Sciences, Paul Scherrer Institute, Forschungsstrasse 111, 5232 Villigen, Switzerland.
⁶ Laboratory of Radiochemistry, Paul Scherrer Institute, Forschungsstrasse 111, 5232 Villigen, Switzerland.
⁷ Institute of Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8A, 1090 Vienna, Austria.
⁸ Research Cluster "Translational Cancer Therapy Research", Waehringer Strasse 42, 1090 Vienna, Austria.

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

Grants and funding

This research received no external funding but the Open Access Funding by the University of Vienna. P. Heffeter was supported by a research grant from the Fellinger Krebsforschungs fonds.