Evaluation of the Therapeutic and Diagnostic Effects of PEGylated Liposome-Embedded Re-188 on Human Non-Small Cell Lung Cancer Using an Orthotopic Small-Animal Model

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Title:	Evaluation of the Therapeutic and Diagnostic Effects of PEGylated Liposome-Embedded Re-188 on Human Non-Small Cell Lung Cancer Using an Orthotopic Small-Animal Model
Authors:	Lin, Liang-Ting Chang, Chih-Hsien Yu, Hsiang-Lin Liu, Ren-Shyan Wang, Hsin-Ell Chiu, Shu-Jun Chen, Fu-Du Lee, Te-Wei Lee, Yi-Jang
Contributors:	生科所
Keywords:	NSCLC nanoradiopharmaceuticals Re-188 SPECT/CT pharmacokinetics
Date:	2014-11
Issue Date:	2015-01-20 09:55:36 (UTC+8)
Abstract:	Non-small cell lung cancer (Nscp 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 Re-188 in PEGylated (PEG is polyethylene glycol) liposomes and investigated the biodistribution, pharrnacokinetics, 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. Re-188 was conjugated to N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA) and loaded into the PEGylated liposome to form a Re-188-liposome. The tumor growth rates and localizations were confirmed using bioluminescent imaging and SPECT/CT after the Re-188-BMEDA or Re-188-liposome was intravenously injected. The accumulation of the nanodrug in various organs 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 Re-188-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 Re-188-liposome was longer than that of Re-188-BMEDA. In an orthotopic tumor model, ex vivo y counting revealed that the uptake of Re-188-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 Re-188-liposome. The life span of Re-188-liposome-treated mice was 2-fold longer than that of untreated control mice. Conclusion: The results of biodistribution, pharmacokinetics, estimated dosimetry, nano-SPECT/CT, and bioluminescent imaging suggest that the PEGylated liposome embedded Re-188 could be used for the treatment of human lung cancers
Relation:	JOURNAL OF NUCLEAR MEDICINE 卷: 55 期: 11 頁碼: 1864-1870
Appears in Collections:	[Graduate Institute of Biotechnology ] journal articles

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