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標題: Pharmacokinetics, dosimetry and comparative efficacy of Re-188-liposome and 5-FU in a CT26-luc lung-metastatic mice model
作者: Chen, L.C.
Wu, Y.H.
Liu, I.H.
Ho, C.L.
Lee, W.C.
Chang, C.H.
Lan, K.L.
Ting, G.
Lee, T.W.
Shien, J.H.
關鍵字: Re-188;Nanoliposome delivery;Pharmacokinetics;Dosimetry;Radiotherapeutics;pegylated liposomal doxorubicin;internal radiotherapy;therapeutic-efficacy;xenograft model;animal-model;cancer;biodistribution;re-188-(dxr)-liposome;re-188-bmeda-liposome;radiopharmaceuticals
Project: Nuclear Medicine and Biology
期刊/報告no:: Nuclear Medicine and Biology, Volume 39, Issue 1, Page(s) 35-43.
The biodistribution, pharmacokinetics, dosimetry and comparative therapeutic efficacy of intravenously administrated Re-188-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposome (Re-188-liposome) and 5-FU were investigated in a CT26-luc lung-metastatic model. After intravenous administration of Re-188-liposome, tumor accumulation from the radioactivity was observed. Levels of radioactivity in tumors were maintained at steady levels (from 5.40 to 5.67 %ID/g) after 4 to 24 h. In pharmacokinetics, the AUC((0 ->infinity)) and MRT(0 ->infinity) and Cl of Re-188-liposome in blood via intravenous route were 998 h %ID/ml, 28.7 h and 0.1 ml/h, respectively. The total excreted fractions of feces and urine were 0.61 and 0.26, respectively. Absorbed doses for Re-188-liposome in the liver and red marrow were 0.31 and 0.08 mSv/MBq, respectively. Tumor-absorbed closes for Re-188-liposome ranged from 48.4 to 1.73 mGy/MBq at 10 to 300 g tumor spheres. In therapeutic efficacy, the survival times of mice after Re-188-liposome [80% maximum tolerated dose (MTD);29.6 MBq], 5-FU (80% MTD; 144 mg/kg), liposome or normal saline treatments were evaluated. Consequently, radiotherapeutics of Re-188-liposome attained a longer lifespan (increase of 34.9%; P=.005) in mice than in the normal saline group. The increase in lifespan of the Re-188-liposome group was 2.5-fold greater than that of the 5-FU group. Therefore, intravenous administration of Re-188-liposome could provide a benefit and it is a promising strategy for delivery of passive nanotargeted radiotherapeutics in oncology applications. (C) 2012 Elsevier Inc. All rights reserved.
ISSN: 0969-8051
DOI: 10.1016/j.nucmedbio.2011.06.010
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