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

Autor:	Happl B; Ludwig Boltzmann Institute Applied Diagnostics, General Hospital of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. thomas.mindt@univie.ac.at.; Division of Nuclear Medicine, Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.; Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Josef-Holaubek-Platz 2 and Währinger Straße 42, 1090 Vienna, Austria., Balber T; Ludwig Boltzmann Institute Applied Diagnostics, General Hospital of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. thomas.mindt@univie.ac.at.; Division of Nuclear Medicine, Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.; Joint Applied Medicinal Radiochemistry Facility of the University of Vienna and the Medical University of Vienna, Vienna, Austria., Heffeter P; Center for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8A, 1090 Vienna, Austria.; Research cluster 'Translational Cancer Therapy Research', Währinger Straße 42, 1090 Vienna, Austria., Denk C; Institute of Applied Synthetic Chemistry, Technische Universität (TU) Wien, Getreidemarkt 9, 1060 Vienna, Austria.; Center for Labelling and Isotope Production, TRIGA Center Atominstitut, TU Wien, Vienna, Austria., Welch JM; Center for Labelling and Isotope Production, TRIGA Center Atominstitut, TU Wien, Vienna, Austria., Köster U; Institut Laue-Langevin, 71 avenue des Martyrs, 38042 Grenoble Cedex 9, France., Alliot C; GIP ARRONAX, 1 rue Aronnax, CS10112, 44817, Saint-Herblain Cedex, France.; CRCI2NA, Inserm/CNRS/Nantes Université, 8 quai Moncousu, 44007, Nantes Cedex 1, France., Bonraisin AC; GIP ARRONAX, 1 rue Aronnax, CS10112, 44817, Saint-Herblain Cedex, France., Brandt M; Ludwig Boltzmann Institute Applied Diagnostics, General Hospital of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. thomas.mindt@univie.ac.at.; Division of Nuclear Medicine, Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.; Joint Applied Medicinal Radiochemistry Facility of the University of Vienna and the Medical University of Vienna, Vienna, Austria., Haddad F; GIP ARRONAX, 1 rue Aronnax, CS10112, 44817, Saint-Herblain Cedex, France.; Laboratoire Subatech, UMR 6457, IMT Nantes Atlantique/CNRS-IN2P3/Nantes Université, 4 Rue A. Kastler, BP 20722, 44307, Nantes Cedex 3, France., Sterba JH; Center for Labelling and Isotope Production, TRIGA Center Atominstitut, TU Wien, Vienna, Austria., Kandioller W; Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Josef-Holaubek-Platz 2 and Währinger Straße 42, 1090 Vienna, Austria.; Research cluster 'Translational Cancer Therapy Research', Währinger Straße 42, 1090 Vienna, Austria., Mitterhauser M; Ludwig Boltzmann Institute Applied Diagnostics, General Hospital of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. thomas.mindt@univie.ac.at.; Division of Nuclear Medicine, Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.; Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Josef-Holaubek-Platz 2 and Währinger Straße 42, 1090 Vienna, Austria.; Joint Applied Medicinal Radiochemistry Facility of the University of Vienna and the Medical University of Vienna, Vienna, Austria., Hacker M; Division of Nuclear Medicine, Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria., Keppler BK; Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Josef-Holaubek-Platz 2 and Währinger Straße 42, 1090 Vienna, Austria.; Research cluster 'Translational Cancer Therapy Research', Währinger Straße 42, 1090 Vienna, Austria., Mindt TL; Ludwig Boltzmann Institute Applied Diagnostics, General Hospital of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. thomas.mindt@univie.ac.at.; Division of Nuclear Medicine, Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.; Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Josef-Holaubek-Platz 2 and Währinger Straße 42, 1090 Vienna, Austria.; Joint Applied Medicinal Radiochemistry Facility of the University of Vienna and the Medical University of Vienna, Vienna, Austria.
Jazyk:	angličtina
Zdroj:	Dalton transactions (Cambridge, England : 2003) [Dalton Trans] 2024 Mar 26; Vol. 53 (13), pp. 6031-6040. Date of Electronic Publication: 2024 Mar 26.
DOI:	10.1039/d4dt00118d
Abstrakt:	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.) [ 97/103 Ru]BOLD-100 were performed with the two ruthenium isotopes ruthenium-103 ( 103 Ru; β - , γ) and ruthenium-97 ( 97 Ru; 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. [ 103 Ru]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. [ 103 Ru]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. [ 97 Ru]BOLD-100.
Databáze:	MEDLINE
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