Production and synthesis of a novel 191Pt-labeled platinum complex and evaluation of its biodistribution in healthy mice

Marina Omokawa; Hiroyuki Kimura; Yuichi Hatsukawa; Hidekazu Kawashima; Kazuaki Tsukada; Yusuke Yagi; Yuki Naito; Hiroyuki Yasui

doi:10.1016/j.bmc.2023.117557

Production and synthesis of a novel ¹⁹¹Pt-labeled platinum complex and evaluation of its biodistribution in healthy mice

Bioorg Med Chem. 2024 Jan 1:97:117557. doi: 10.1016/j.bmc.2023.117557. Epub 2023 Dec 9.

Authors

Marina Omokawa¹, Hiroyuki Kimura², Yuichi Hatsukawa³, Hidekazu Kawashima⁴, Kazuaki Tsukada⁵, Yusuke Yagi⁶, Yuki Naito¹, Hiroyuki Yasui¹

Affiliations

¹ Laboratory of Analytical and Bioinorganic Chemistry, Division of Analytical and Physical Sciences, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
² Laboratory of Analytical and Bioinorganic Chemistry, Division of Analytical and Physical Sciences, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan; Division of Probe Chemistry for Disease Analysis/Central Institute for Radioisotope Science, Research Center for Experimental Modeling of Human Disease, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8640, Japan. Electronic address: hkimura@staff.kanazawa-u.ac.jp.
³ National Institute for Quantum and Radiological Science and Technology (QST), Tokai, Ibaraki 319-1195, Japan.
⁴ Radioisotope Research Center, Kyoto Pharmaceutical University, 1 Shichono-cho, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.
⁵ Japan Atomic Energy Agency, Tokai, Ibaraki 319-1105 Japan.
⁶ Department of Radiological Technology, Faculty of Medicinal Science, Kyoto College of Medical Science, 1-3 Imakita, Oyama-higashi, Sonobe, Nantan, Kyoto 622-0041, Japan.

PMID: 38086274
DOI: 10.1016/j.bmc.2023.117557

Abstract

We previously reported that our sugar-conjugated platinum complex (cis-dichloro [(2-fluoro-α-d-glucopylanosidyl) propane-1,3-diamine] platinum: FGC-Pt) has low toxicity and tumor growth inhibitory effect comparable to that of cisplatin. We focused on radioactive Pt isotopes in order to analyze the kinetics of FGC-Pt using gamma-ray imaging techniques, assuming that FGC-Pt could be used for chemotherapy in the future. Therefore, in this study, we aimed to develop a non-invasive method to analyze the biodistribution of FGC-Pt using ¹⁹¹Pt-labeled FGC-Pt ([¹⁹¹Pt]FGC-Pt). ¹⁹¹Pt was produced via the (n,2n) reaction induced by accelerator neutrons. [¹⁹¹Pt]FGC-Pt was prepared using two different methods. In the first method, [¹⁹¹Pt]FGC-Pt (method A) was obtained through the accelerator neutron irradiation of FGC-Pt. In the second method, [¹⁹¹Pt]FGC-Pt (method B) was synthesized using [¹⁹¹Pt]K₂PtCl₄, which was obtained by the accelerator neutron irradiation of K₂PtCl₄. Highly purified [¹⁹¹Pt]FGC-Pt was obtained using the latter method, which suggests that the synthetic method using a ¹⁹¹Pt-labeled platinum reagent is suitable for the radioactivation of platinum complexes. We also aimed to investigate whether a significant correlation existed between the biodistribution of FGC-Pt and [¹⁹¹Pt]FGC-Pt in healthy mice 24 h after tail vein administration. FGC-Pt and [¹⁹¹Pt]FGC-Pt were similarly distributed in healthy mice, with a higher accumulation in the liver and kidney 24 h post injection. In addition, a significant correlation (p < 0.05, r = 0.92) between the ¹⁹¹Pt radioactivity concentration (%ID/g (gamma counter)) and platinum concentration (%ID/g (ICP-MS)) was observed in 13 organs. These results suggest that ¹⁹¹Pt-labeled compounds, synthesized using radioactive platinum reagents, can be used to confirm the biodistribution of platinum compounds. Our study on the biodistribution of [¹⁹¹Pt]FGC-Pt is expected to contribute to the development of novel platinum-based drugs in the future.

Keywords: (191)Pt labeled platinum complex; Biodistribution of platinum complex; Platinum complex.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents* / pharmacology
Cisplatin / pharmacology
Mice
Neoplasms* / drug therapy
Platinum
Radioisotopes
Tissue Distribution

Substances

Platinum
Cisplatin
Antineoplastic Agents
Radioisotopes