Journal
CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
Volume 24, Issue 4, Pages 453-460Publisher
MARY ANN LIEBERT INC
DOI: 10.1089/cbr.2008.0572
Keywords
ascites; C26/tk-luc tumor; indium-111; micro-PET; PEGylated liposomes
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Funding
- National Health Research Institutes (Miaoli, Taiwan, ROC) [96A1-NMPP01-007, 97A1-NMPP01-007]
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Nanoliposomes are important drug carriers that can passively target tumor sites by the enhanced permeability and retention (EPR) effect in neoplasm lesions. This study evaluated the biodistribution and pharmacokinetics of In-111-labeled vinorelbine (VNB)-encapsulated PEGylated liposomes (IVNBPL) after intraperitoneal (i.p.) and intravenous (i.v.) administration in a C26/tk-luc colon carcinoma ascites mouse model. IVNBPL was prepared by labeling VNB-encapsulated PEGylated liposomes with In-111-oxine. BALB/c mice were i.p. inoculated with 2x10(5) C26/tk-luc cells in 500 mu L of phosphate-buffered saline. Peritoneal tumor lesions were confirmed by I-124-FIAU/micro-PET (positron emission tomography) and bioluminescence imaging. Ascites production was examined by ultrasound imaging on day 10 after tumor cell inoculation. The pharmacokinetics and biodistribution studies of IVNBPL in a tumor/ascites mouse model were conducted. The labeling efficiency was more than 90%. The in vitro stability in human plasma at 37 degrees C for 72 hours was 83% +/- 3.5%. For i.p. administration, the areas under curves (AUCs) of ascites and tumor were 6.78- and 1.70-fold higher, whereas the AUCs of normal tissues were lower than those via the i.v. route. This study demonstrates that i.p. administration is a better approach than i.v. injection for IVNBPL, when applied to the treatment of i.p. malignant disease in a tumor/ascites mouse model.
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