MR Reporter Gene Imaging of Endostatin Expression and Therapy
- 3 December 2009
- journal article
- research article
- Published by Springer Nature in Molecular Imaging & Biology
- Vol. 12 (5), 520-529
- https://doi.org/10.1007/s11307-009-0286-0
Abstract
Purpose The aim of this study is to monitor endostatin gene expression and therapy using transferrin receptor (TfR) as reporter gene and transferrin conjugate of ultrasmall supramagnetic iron oxide nanoparticle (Tf–USPIO) as magnetic resonance (MR) reporter probe. Procedure A retroviral plasmid (pLP-LNCX) encoding mouse endostatin and TfR was constructed, and packaged with a titer of 4 × 107colony-forming units per millimeter. MDA-MB-231 breast tumors were established in BALB/c mice by subcutaneous injection of 2 × 106 MDA-MB-231 cells. Mice were intratumorally injected with recombinant retrovirus and imaged with MR using Tf–USPIO. Western blot, Prussian blue, and immunohistochemical staining were performed to validate the magnetic resonance imaging results. The antitumor effect of retro-endostatin (ES)-TfR was also evaluated by intratumoral injection of the viral vector. Results The expression of both endostatin and TfR genes in MDA-MB-231 cells after retroviral transfection was confirmed by Western blot and flow cytometry. Tf–USPIO conjugate binds specifically to cells stably transfected with retro-ES-TfR. After intravenous injection of the Tf–USPIO conjugate, there was a more pronounced decrease in T2 relaxation time in tumors treated with retro-ES-TfR than in tumors treated with empty retrovirus retro-LNCX. The expression of ES gene significantly delayed the growth of MDA-MB-231 tumor and reduction of microvessel density and VEGF level as compared to those without viral transfection or transfected with empty retro-LNCX vector. Conclusions Endostatin therapeutic gene expression was visualized successfully using TfR reporter gene and Tf–USPIO MR reporter probe, which indicates that MR reporter gene imaging may be valuable in gene therapy to evaluate therapeutic gene expression and treatment efficacy.Keywords
This publication has 43 references indexed in Scilit:
- Comparison of Viral and Nonviral Vectors for Gene Transfer to Human Endothelial Progenitor CellsTissue Engineering, Part C: Methods, 2009
- Gene Therapy in Orthotopic Lung Cancer Murine Model with Angiogenesis Inhibitor, EndostatinHuman Gene Therapy, 2008
- Size, charge and concentration dependent uptake of iron oxide particles by non-phagocytic cellsBiomaterials, 2008
- Ultrasmall c(RGDyK)-Coated Fe3O4 Nanoparticles and Their Specific Targeting to Integrin αvβ3-Rich Tumor CellsJournal of the American Chemical Society, 2008
- Endostatin gene therapy enhances the efficacy of paclitaxel to suppress breast cancers and metastases in miceJournal of Biomedical Science, 2007
- Gene transfer of endostatin enhances the efficacy of doxorubicin to suppress human hepatocellular carcinomas in miceCancer Science, 2007
- Anti‐tumor effect of endostatin mediated by retroviral gene transfer in mice bearing renal cell carcinomaThe FASEB Journal, 2007
- Antitumor efficacy improved by local delivery of species-specific endostatinJournal of Neurosurgery, 2006
- Recombinant human endostatin administered as a 28-day continuous intravenous infusion, followed by daily subcutaneous injections: a phase I and pharmacokinetic study in patients with advanced cancerAnnals of Oncology, 2005
- Induction of therapeutic antitumor antiangiogenesis by intratumoral injection of genetically engineered endostatin-producing Semliki Forest virusCancer Gene Therapy, 2001