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

We previously reported that our sugar-conjugated platinum complex (cis-dichloro [(2-fluoro-alpha-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 Pt-191-labeled FGC-Pt ([Pt-191]FGC-Pt). Pt- 191 was produced via the (n,2n) reaction induced by accelerator neutrons. [Pt-191]FGC-Pt was prepared using two different methods. In the first method, [Pt-191]FGC-Pt (method A) was obtained through the accelerator neutron irradiation of FGC-Pt. In the second method, [Pt-191]FGC-Pt (method B) was synthesized using [Pt-191]K2PtCl4, which was obtained by the accelerator neutron irradiation of K2PtCl4. Highly purified [Pt-191]FGC-Pt was obtained using the latter method, which suggests that the synthetic method using a Pt-191-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 [Pt-191]FGC-Pt in healthy mice 24 h after tail vein administration. FGC-Pt and [Pt-191]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 Pt-191 radioactivity concentration (%ID/g (gamma counter)) and platinum concentration (%ID/g (ICP-MS)) was observed in 13 organs. These results suggest that Pt-191-labeled compounds, synthesized using radioactive platinum reagents, can be used to confirm the biodistribution of platinum compounds. Our study on the biodistribution of [Pt-191]FGC-Pt is expected to contribute to the development of novel platinum-based drugs in the future.