Evaluation of the therapeutic and diagnostic effects of PEGylated liposome-embedded 188re on human non-small cell lung cancer using an orthotopic small-animal model

Liang Ting Lin, Chih Hsien Chang, Hsiang Lin Yu, Ren Shyan Liu, Hsin Ell Wang, Shu Jun Chiu, Fu Du Chen, Te Wei Lee, Yi Jang Lee*

*此作品的通信作者

研究成果: Article同行評審

29 引文 斯高帕斯(Scopus)

摘要

Non-small cell lung cancer (NSCLC) is a highly morbid and mortal cancer type that is difficult to eradicate using conventional chemotherapy and radiotherapy. Little is known about whether radionuclide-based pharmaceuticals can be used for treating NSCLC. Here we embedded the therapeutic radionuclide 188Re in PEGylated (PEG is polyethylene glycol) liposomes and investigated the biodistribution, pharmacokinetics, and therapeutic efficacy of this nanoradiopharmaceutical on NSCLC using a xenograft lung tumor model and the reporter gene imaging techniques. Methods: Human NSCLC NCI-H292 cells expressing multiple reporter genes were used in this study. 188Re was conjugated to N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA) and loaded into the PEGylated liposome to form a 188Reliposome. The tumor growth rates and localizations were confirmed using bioluminescent imaging and SPECT/CT after the 188Re-BMEDA or 188Re-liposome was intravenously injected. The accumulation of the nanodrug in various organ was determined by the biodistribution analysis and the nano-SPECT/CT system. The pharmacokinetic and dosimetric analyses were further determined using WinNonlin and OLINDA/EXM, respectively. Results: The biodistribution and nano- SPECT/CT imaging showed that PEGylated 188Re-liposome could efficiently accumulate in xenograft tumors formed by NCI-H292 cells that were subcutaneously implanted in nude mice. Pharmacokinetic analysis also showed that the retention of 188Re-liposome was longer than that of 188Re-BMEDA. In an orthotopic tumor model, ex vivo γ counting revealed that the uptake of 188Re-liposome was detected in tumor lesions but not in surrounding normal lung tissues. Moreover, we evaluated the therapeutic efficacy using bioluminescent imaging and showed that the lung tumor growth was suppressed but not eradicated by 188Re-liposome. The life span of 188Re-liposome- treated mice was 2-fold longer than that of untreated control mice. Conclusion: The results of biodistribution, pharmacokinetics, est mated dosimetry, nano-SPECT/CT, and bioluminescent imaging suggest that the PEGylated liposome-embedded 188Re could be used for the treatment of human lung cancers.

原文English
頁(從 - 到)1864-1870
頁數7
期刊Journal of Nuclear Medicine
55
發行號11
DOIs
出版狀態Published - 1 11月 2014

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