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64Cu2+ Complexes of Tripodal Amine Ligands on In Vivo Tumor and Liver Uptake and Intracellular Cu Distribution in the Extrahepatic Bile Duct Carcinoma Cell Line TFK-1: A Basic Comparative Study
Shinada, M.; Takahashi, M.; Igarashi, C.; Matsumoto, H.; Hihara, F.; Tachibana, T.; Oikawa, M.; Suzuki, H.; Zhang, M.-R.; Higashi, T.; Kurihara, H.; Yoshii, Y.; Doi, Y. 64Cu2+ Complexes of Tripodal Amine Ligands’ In Vivo Tumor and Liver Uptakes and Intracellular Cu Distribution in the Extrahepatic Bile Duct Carcinoma Cell Line TFK-1: A Basic Comparative Study. Pharmaceuticals2024, 17, 820.
Shinada, M.; Takahashi, M.; Igarashi, C.; Matsumoto, H.; Hihara, F.; Tachibana, T.; Oikawa, M.; Suzuki, H.; Zhang, M.-R.; Higashi, T.; Kurihara, H.; Yoshii, Y.; Doi, Y. 64Cu2+ Complexes of Tripodal Amine Ligands’ In Vivo Tumor and Liver Uptakes and Intracellular Cu Distribution in the Extrahepatic Bile Duct Carcinoma Cell Line TFK-1: A Basic Comparative Study. Pharmaceuticals 2024, 17, 820.
Shinada, M.; Takahashi, M.; Igarashi, C.; Matsumoto, H.; Hihara, F.; Tachibana, T.; Oikawa, M.; Suzuki, H.; Zhang, M.-R.; Higashi, T.; Kurihara, H.; Yoshii, Y.; Doi, Y. 64Cu2+ Complexes of Tripodal Amine Ligands’ In Vivo Tumor and Liver Uptakes and Intracellular Cu Distribution in the Extrahepatic Bile Duct Carcinoma Cell Line TFK-1: A Basic Comparative Study. Pharmaceuticals2024, 17, 820.
Shinada, M.; Takahashi, M.; Igarashi, C.; Matsumoto, H.; Hihara, F.; Tachibana, T.; Oikawa, M.; Suzuki, H.; Zhang, M.-R.; Higashi, T.; Kurihara, H.; Yoshii, Y.; Doi, Y. 64Cu2+ Complexes of Tripodal Amine Ligands’ In Vivo Tumor and Liver Uptakes and Intracellular Cu Distribution in the Extrahepatic Bile Duct Carcinoma Cell Line TFK-1: A Basic Comparative Study. Pharmaceuticals 2024, 17, 820.
Abstract
Copper (Cu) is a critical element for cancer cell proliferation and considerably accumulates in the nucleus. 64Cu2+ is an anticancer radiopharmaceuticals targeting the copper requirement of cancer cells. However, intravenously injected 64Cu2+ ions primarily accumulate in the liver. Ligand complexation of 64Cu2+ would be a promising method for increasing tumor delivery by reducing liver uptake. Herein, we used three tripodal amine ligands [tris(2-aminoethyl)amine (Tren), diethylenetriamine (Dien), and tris(2-pyridylmethyl)amine (TPMA)] to enclose 64Cu2+ ions and compared their in vivo tumor and liver uptake using a tumor-bearing xenograft mouse model of the extrahepatic bile duct carcinoma cell line TFK-1. We examined intracellular Cu distribution using microparticle-induced X-ray emission (micro-PIXE) analysis for these compounds. 64Cu2+-Tren and 64Cu2+-Dien showed higher tumor uptake than 64Cu2+-TPMA and 64Cu2+ ions in TFK-1 tumors. Among the three 64Cu2+ complexes and 64Cu2+ ions, liver uptake was inversely correlated with tumor uptake. Micro-PIXE analysis showed that in vitro cellular uptake was similar to in vivo tumor uptake and nuclear delivery was the highest for 64Cu2+-Tren. Conclusively, an inverse correlation between tumor and liver uptake was observed using three 64Cu2+ complexes of tripodal amine ligands and 64Cu2+ ions. These results provide useful information for the future development of anticancer 64Cu radiopharmaceuticals.
Medicine and Pharmacology, Medicine and Pharmacology
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