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| Title: | Biodistribution and pharmacokinetics of (188)Re-liposomes and their comparative therapeutic efficacy with 5-fluorouracil in C26 colonic peritoneal carcinomatosis mice |
| Authors: | Tsai, CC;Chang, CH;Chen, LC;Chang, YJ;Lan, KL;Wu, YH;Hsu, CW;Liu, IH;Ho, CL;Lee, WC;Ni, HC;Chang, TJ;Ting, G;Lee, TW |
| Contributors: | National Institute of Cancer Research |
| Abstract: | Background: Nanoliposomes are designed as carriers capable of packaging drugs through passive targeting tumor sites by enhanced permeability and retention (EPR) effects. In the present study the biodistribution, pharmacokinetics, micro single-photon emission computed tomography (micro-SPECT/CT) image, dosimetry, and therapeutic efficacy of (188)Re-labeled nanoliposomes ((188)Re-liposomes) in a C26 colonic peritoneal carcinomatosis mouse model were evaluated. Methods: Colon carcinoma peritoneal metastatic BALB/c mice were intravenously administered 188Re-liposomes. Biodistribution and micro-SPECT/CT imaging were performed to determine the drug profile and targeting efficiency of 188Re-liposomes. Pharmacokinetics study was described by a noncompartmental model. The OLINDA vertical bar EXM (R) computer program was used for the dosimetry evaluation. For therapeutic efficacy, the survival, tumor, and ascites inhibition of mice after treatment with 188Re-liposomes and 5-fluorouracil (5-FU), respectively, were evaluated and compared. Results: In biodistribution, the highest uptake of 188Re-liposomes in tumor tissues (7.91% +/- 2.02% of the injected dose per gram of tissue [%ID/g]) and a high tumor to muscle ratio (25.8 +/- 6.1) were observed at 24 hours after intravenous administration. The pharmacokinetics of 188Re-liposomes showed high circulation time and high bioavailability (mean residence time [MRT] = 19.2 hours, area under the curve [AUC] = 820.4%ID/g*h). Micro-SPECT/CT imaging of (188)Re-liposomes showed a high uptake and targeting in ascites, liver, spleen, and tumor. The results were correlated with images from autoradiography and biodistribution data. Dosimetry study revealed that the (188)Re-liposomes did not cause high absorbed doses in normal tissue but did in small tumors. Radiotherapeutics with (188)Re-liposomes provided better survival time (increased by 34.6% of life span; P < 0.05), tumor and ascites inhibition (decreased by 63.4% and 83.3% at 7 days after treatment; P < 0.05) in mice compared with chemotherapeutics of 5-fluorouracil (5-FU). Conclusion: The use of (188)Re-liposomes for passively targeted tumor therapy had greater therapeutic effect than the currently clinically applied chemotherapeutics drug 5-FU in a colonic peritoneal carcinomatosis mouse model. This result suggests that (188)Re-liposomes have potential benefit and are safe in treating peritoneal carcinomatasis of colon cancer. |
| Date: | 2011-10 |
| Relation: | International Journal of Nanomedicine. 2011 Oct;6:2607-2619. |
| Link to: | http://dx.doi.org/10.2147/ijn.s23834 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1178-2013&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000297681900001 |
| Appears in Collections: | [其他] 期刊論文
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| ISI000297681900001.pdf | | 1367Kb | Adobe PDF | 375 | View/Open |
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