Pharmacokinetics and Dosimetry of111In/188Re-Labeled PEGylated Liposomal Drugs in Two Colon Carcinoma-Bearing Mouse Models
| Autor: | Fu Du Chen, Yi-Yu Lin, Hsin Ell Wang, Ya-Jen Chang, Michael G. Stabin, Wuu-Jyh Lin, Liang-Cheng Chen, Te-Wei Lee, Cheng Allen Chang, Chih-Hsien Chang, Yun Long Tseng, Gann Ting, Ming-Hsien Lin, Jia-Je Li |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Cancer Research Biodistribution Enhanced permeability and retention effect Pharmacology Polyethylene Glycols Mice Pharmacokinetics Cell Line Tumor medicine Animals Humans Distribution (pharmacology) Infusions Parenteral Tissue Distribution Radiology Nuclear Medicine and imaging Doxorubicin Radiometry Radioisotopes Mice Inbred BALB C Liposome business.industry Indium Radioisotopes Original Articles General Medicine Rhenium Oncology Colonic Neoplasms Radionuclide therapy Drug carrier business Neoplasm Transplantation medicine.drug |
| Zdroj: | Cancer Biotherapy and Radiopharmaceuticals. 26:373-380 |
| ISSN: | 1557-8852 1084-9785 |
| DOI: | 10.1089/cbr.2010.0906 |
| Popis: | PEGylated liposomes are important drug carriers for nanomedicine cancer therapy. PEGylated liposomes can encapsulate radio- and chemo-drugs and passively target tumor sites via enhanced permeability and retention effect. This study estimated the pharmacokinetics and dosimetry after administration of radio-chemotherapeutics ((111)In-labeled vinorelbine [VNB]-encapsulated liposomes, InVNBL, and (188)Re-labeled doxorubicin [DXR]-encapsulated liposomes, ReDXRL) for radionuclide therapy in two colon carcinoma-bearing mouse models. A C26 colon carcinoma tumor/ascites mouse model and a subcutaneous solid tumor-bearing mouse model were employed. Biodistribution studies of InVNBL and ReDXRL after intraperitoneal administration in tumor/ascites-bearing mice (protocol A) and intravenous administration in subcutaneous solid tumor-bearing mice (protocol B) were performed. The radiation dose to normal tissues and tumors were calculated based on the results of distribution studies in mice, using the OLINDA/EXM program. The cumulated activities in most organs after administration of InVNBL in either the tumor/ascites-bearing mice (protocol A) or the subcutaneous solid tumor-bearing mice (protocol B) were higher than those of ReDXRL. Higher tumor-to-normal-tissues absorption dose ratios (T/NTs) were observed after administration of InVNBL than those of ReDXRL for protocol A. The T/NTs for the liver, spleen, and red marrow after injection of InVNBL for protocol B were similar to those of ReDXRL. The critical organ was found to be red marrow, and thus the red marrow absorption dose defined the recommended maximum administration activity of these liposomal drugs. Characterization of pharmacokinetics and dosimetry is needed to select the appropriate radiotherapeutics for specific tumor treatment applications. The results suggest that InVNBL is a promising therapeutic agent, which is as good as ReDXRL, in two mouse tumor models. |
| Databáze: | OpenAIRE |
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