Therapeutic Efficacy Evaluation of 111In-VNB-liposome on Human Colorectal Adenocarcinoma HT-29/luc Mouse Xenografts

Autor: Wan-Chi Lee, 李婉綺
Rok vydání: 2005
Druh dokumentu: 學位論文 ; thesis
Popis: 93
Objective To evaluate the therapeutic efficacy of the liposome encaged with vinorelbine (VNB) and 111In-oxine on human colorectal adenocarcinoma (HT-29) using HT-29/luc mouse xenograft. Multimodalities include biodistribution, whole-body autoradiography (WBAR), gamma scintigraphy and bioluminescence optical imaging (BLI) were applied. Materials and Methods HT-29 cells were stably transfected with plasmid vectors containing luciferase gene (luc), and were transplanted to the male NOD/SCID mice. When tumor size reached 500-600 mm3, biodistribution of the drug was studied. At various time post 111In-VNB-liposome injection, mice were sacrificed and assayed. The uptake of 111In-VNB-liposome in tumor and normal tissues/organs were calculated. On the other hand, BLI using Xenogen IVIS50, gamma scinitigraphy and WBAR were used to evaluate the therapeutic efficacy when tumor size was about 100 mm3. Results The tumor/blood ratios of 111In-VNB-liposome were 0.044, 0.058, 2.690, 20.628 and 24.327, respevtively, at 1, 4, 24, 48 and 72 hrs post injection. Gamma scinitigraphy showed that the tumor/muscle ratios were 2.04, 2.25, and 4.39, respectively, at 0, 5 and 10 mg/kg VNB. BLI showed that significant tumor control was achieved in the group of 10 mg/kg VNB, but not in other groups. WBAR also confirmed this result. Conclusions We have successfully established a non-invasive imaging system for the evaluation of therapeutic effectiveness of new developed drugs or new therapeutic trials. Efficacy studies carried on SCID mice bearing HT-29/luc tumors indicated that 111In-VNB-liposome was effective for tumor growth reduction. This study demonstrates the benefit and potential application of a multimodality imaging system in therapeutic and diagnostic strategies to evaluate drug or treatment efficacy, and may also apply to other fields of biomedical research.
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