| Summary: | 碩士 === 國立清華大學 === 生醫工程與環境科學系 === 98 === Vascular endothelial growth factor (VEGF) is one of important key factors of angiogenesis which is often expressed by a variety of tumors. In this study, we have developed an immunoliposome (IL) system that a liposome was pegylated and conjugated with bevacizumab, a humanized anti-VEGF monoclonal antibody. In this drug delivery system, the fabricated immunoliposome was of a nanoparticle that could passive retention in a variety of tumors through enhanced permeability and retention effect (EPR effect), with a size around 100 nm where bevacizumab could act a function targeting to VEGF for cancer cell. Furthermore, the immunoliposome was encapsulated with the radionuclide, indium-111 via DTPA as the complexing agent for imaging purpose. Human colorectal cancer cell, LS174T with overexpression of VEGF was adopted as the targeting cell in this work. An animal model bearing the tumor was used for the in vivo biodistribution and imaging studies.
Methods: The 111In entrapped immunoliposome, bevacizumab-111In- liposome (abbreviated as Bev-111In-liposome) and 111In entrapped liposome, 111In-liposome were prepared. The Bev-111In-liposome and 111In-liposome were subjected to administrate respectively into the LS174T tumor bearing mice via the tail vein. Biodistribution and microSPECT/CT imaging were carried out at the following postinjection times, 1, 4, 8, 24, 48, 72 and 96 h. Pharmacokinetics was simultaneously studied along with the postinjection times, 0.25, 0.5, 1, 4, 6, 24, 48, 72, 96, and 168 h.
Results: The in vitro stability study indicated that Bev-111In-liposome was quite stable either in both normal saline and rat plasma for a significant long time, i.e., at least 120 h. For pharmacokinetics study, the the t1/2α (initial redistribution phase with a short half-life) and t1/2β (elimination phase with a longer half-life) of Bev-111In-liposome were 0.666 and 13.975 h, respectively. The tumor uptake could reach maximum at 24 h postinjection, at 15.3±3.66 %ID/g for 111In-liposome and at 14.24±3.59 %ID/g for Bev-111In- liposomes, respectively. The results of microSPECT/CT imaging showed that the immunoactive liposome could clearly target the tumor at l h, i.e., much earlier than the passive liposome at 24 h.
Conclusions: Both of 111In-liposome and Bev-111In-liposome showed the potentiality as a diagnostic agent in the study using the VEGF overexpressive tumor, LS174T bearing mouse model. However, Bev-111In-Liposome could detect the localization of the tumor as early as at 1 h while much later for the 111In-Liposome.
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