Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/80760
Title: PEGylated liposome-encapsulated rhenium-188 radiopharmaceutical inhibits proliferation and epithelial-mesenchymal transition of human head and neck cancer cells in vivo with repeated therapy
Authors: Chang, CY
Chen, CC
Lin, LT 
Chang, CH
Chen, LC
Wang, HE
Lee, TW
Lee, YJ
Issue Date: 2018
Publisher: Nature Publishing Group
Source: Cell death discovery, 31 Oct. 2018, v. 4, 100, p. 1-13 How to cite?
Journal: Cell death discovery 
Abstract: Human head and neck squamous cell carcinoma (HNSCC) is usually treated with chemoradiotherapy, but the therapeutic efficacy could be hampered by intrinsic radioresistance and early relapse. Repeated administrations of rhenium-188 (Re-188)-conjugated radiopharmaceutical has been reported to escalate the radiation doses for better control of advanced human cancers. Here we found that high dosage of Re-188-liposome, the liposome-encapsulated Re-188 nanoparticles exhibited significant killing effects on HNSCC FaDu cells and SAS cells but not on OECM-1 cells. To investigate the biological and pharmaceutical responses of high Re-188-liposomal dosage in vivo, repeated doses of Re-188-liposome was injected into the orthotopic tumor model. FaDu cells harboring luciferase reporter genes were implanted in the buccal positions of nude mice followed by intravenous injection of Re-188-liposome. The Cerenkov luminescence imaging (CLI) was performed to demonstrate an increased accumulation of Re-188-liposome in the tumor lesion of nude mice with repeated doses compared to a single dose. Repeated doses also enhanced tumor growth delay and elongated the survival of tumor-bearing mice. These observations were associated with significant loss of Ki-67 proliferative marker and epithelial-mesenchymal transition (EMT) markers in excised tumor cells. The body weights of mice were not significantly changed using different doses of Re-188-liposome, yet repeated doses led to lower blood counts than a single dose. Furthermore, the pharmacokinetic analysis showed that the internal circulation of repeated Re-188-liposomal therapy was elongated. The biodistribution analysis also demonstrated that accumulations of(188)Re-liposome in tumor lesions and bone marrow were increased using repeated doses. The absorbed dose of repeated doses over a single dose was about twofold estimated for a 1 g tumor. Together, these data suggest that the radiopharmacotherapy of Re-188-liposome can enhance tumor suppression, survival extension, and internal circulation without acute toxicity using repeated administrations.
URI: http://hdl.handle.net/10397/80760
EISSN: 2058-7716
DOI: 10.1038/s41420-018-0116-8
Rights: © 2018 The Author(s).
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
The following publication Chang, C. Y., Chen, C. C., Lin, L. T., Chang, C. H., Chen, L. C., Wang, H. E., ... & Lee, Y. J. (2018). PEGylated liposome-encapsulated rhenium-188 radiopharmaceutical inhibits proliferation and epithelial–mesenchymal transition of human head and neck cancer cells in vivo with repeated therapy. Cell death discovery, 4(1), 100, 1-13 is available at https://dx.doi.org/10.1038/s41420-018-0116-8
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