Therapeutic efficacy evaluation of 111In-labeled PEGylated liposomal vinorelbine in murine colon carcinoma with multimodalities of molecular imaging
Journal
Journal of Nuclear Medicine
Journal Volume
50
Journal Issue
12
Pages
2073-2081
Date Issued
2009
Author(s)
Chow, T.-H.
Abstract
In our previous studies using combined radioisotopes with chemotherapeutic liposomal drugs (i.e., 111In-labeled polyethylene glycol (PEG)ylated liposomal vinorelbine) we have reported possible therapeutic efficiency in tumor growth suppression. Nevertheless, the challenge remains as to whether this chemotherapy has a therapeutic effect as good as that of combination therapy. The goal of this study was to investigate the real therapeutic effectiveness of 6 mol% PEG 111In-vinorelbine liposomes via the elevation of the radiation dosage and reduction in the concentration of chemotherapeutic agents. Methods: Murine colon carcinoma cells transfected with dual-reporter genes (CT-26/tk-luc) were xenografted into BALB/c mice. The biodistribution was estimated to determine the drug profile and targeting efficiency of 111In-vinorelbine liposomes. Bioluminescence imaging and 18F-FDG small-animal PET were applied to monitor the therapeutic response after drug administration. The survival in vivo was estimated and linked with the toxicologic and histopathologic analyses to determine the preclinical safety and feasibility of the nanomedicine. Results: Effective long-term circulation of radioactivity in the plasma was achieved by 6 mol% PEG 111In-vinorelbine liposomes, and this dose showed significantly lower uptake in the reticuloendothelial system than that of 0.9 mol% PEG 111In-vinorelbine liposomes. Selective tumor uptake was represented by cumulative deposition, and the maximum accumulation was at 48 h after injection. The combination therapy exhibited an additive effect for tumor growth suppression as tracked by caliper measurement, bioluminescence imaging, and small-animal PET. Furthermore, an improved survival rate and reduced tissue toxicity were closely correlated with the toxicologic and histopathologic results. Conclusion: The results demonstrated that the use of 6 mol% PEG 111In-vinorelbine liposomes for passively targeted tumor therapy displayed an additive effect with combined therapy, not only by prolonging the circulation rate because of a reduction in the phagocytic effect of the reticuloendothelial system but also by enhancing tumor uptake. Thus, this preclinical study suggests that 6 mol% PEG 111In-vinorelbine liposomes have the potential to increase the therapeutic index and reduce the toxicity of the passively nanotargeted chemoradiotherapies. Copyright ? 2009 by the Society of Nuclear Medicine, Inc.
Subjects
111In-vinorelbine liposomes; 18F-FDG small-animal PET; Bioluminescence imaging (BLI); CT-26/tk-luc; Reticuloendothelial system (RES)
SDGs
Other Subjects
fluorodeoxyglucose f 18; pegylated liposomal vinorelbine in 111; radiopharmaceutical agent; unclassified drug; diagnostic agent; drug derivative; indium; liposome; macrogol derivative; navelbine; vinblastine; animal experiment; animal tissue; article; Bagg albino mouse; bioluminescence; cancer cell; cancer chemotherapy; cancer inhibition; colon carcinoma; controlled study; drug blood level; drug distribution; drug efficacy; drug safety; drug screening; drug targeting; drug uptake; genetic transfection; histopathology; human; isotope labeling; molecular imaging; mouse; multimodality cancer therapy; nanomedicine; nonhuman; positron emission tomography; priority journal; radiation dose; reticuloendothelial system; survival; toxicology; treatment response; xenograft; animal; body weight; chemistry; colon tumor; dose response; drug effect; isotope labeling; luminescence; metabolism; molecular imaging; pathology; scintiscanning; survival rate; tissue distribution; treatment outcome; tumor cell line; Animals; Body Weight; Cell Line, Tumor; Colonic Neoplasms; Dose-Response Relationship, Drug; Fluorodeoxyglucose F18; Indium Radioisotopes; Isotope Labeling; Liposomes; Luminescent Measurements; Mice; Mice, Inbred BALB C; Molecular Imaging; Polyethylene Glycols; Positron-Emission Tomography; Radiation Dosage; Survival Rate; Tissue Distribution; Treatment Outcome; Vinblastine
Type
journal article