scholarly journals Therapeutic Effect of Sodium Iodide Symporter Gene Therapy Combined With External Beam Radiotherapy and Targeted Drugs That Inhibit DNA Repair

2010 ◽  
Vol 18 (9) ◽  
pp. 1599-1605 ◽  
Author(s):  
Mohan Hingorani ◽  
Christine L White ◽  
Shane Zaidi ◽  
Hardev S Pandha ◽  
Alan A Melcher ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Dna Repair ◽  
Therapeutic Effect ◽  
Sodium Iodide ◽  
External Beam Radiotherapy ◽  
Targeted Drugs ◽  
External Beam ◽  
Sodium Iodide Symporter

scholarly journals Application of 188Rhenium as an Alternative Radionuclide for Treatment of Prostate Cancer after Tumor-Specific Sodium Iodide Symporter Gene Expression

2007 ◽  
Vol 92 (11) ◽  
pp. 4451-4458 ◽  
Author(s):  
Michael J. Willhauck ◽  
Bibi-Rana Sharif Samani ◽  
Franz-Josef Gildehaus ◽  
Ingo Wolf ◽  
Reingard Senekowitsch-Schmidtke ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Therapeutic Effect ◽  
Half Life ◽  
Sodium Iodide ◽  
Specific Antigen ◽  
Volume Reduction ◽  
Sodium Iodide Symporter ◽  
Nis Gene

Abstract Context: We reported recently the induction of iodide accumulation in prostate cancer cells (LNCaP) by prostate-specific antigen promoter-directed sodium iodide symporter (NIS) expression that allowed a significant therapeutic effect of 131iodine (131I). These data demonstrated the potential of the NIS gene as a novel therapeutic gene, although in some extrathyroidal tumors, therapeutic efficacy may be limited by rapid iodide efflux due to a lack of iodide organification. Objective: In the current study, we therefore studied the potential of 188rhenium (188Re), as an alternative radionuclide, also transported by NIS, with a shorter half-life and higher energy β-particles than 131I. Results: NIS-transfected LNCaP cells (NP-1) concentrated 8% of the total applied activity of 188Re as compared with 16% of 125I, which was sufficient for a therapeutic effect in an in vitro clonogenic assay. γ-Camera imaging of NP-1 cell xenografts in nude mice revealed accumulation of 8–16% injected dose (ID)/g 188Re (biological half-life 12.9 h), which resulted in a 4.7-fold increased tumor absorbed dose (450 mGy/MBq) for 188Re as compared with 131I. After application of 55.5 MBq 131I or 188Re, smaller tumors showed a similar average volume reduction of 86%, whereas in larger tumors volume reduction was significantly increased from 73% after 131I treatment to 85% after application of 188Re. Conclusion: Although in smaller prostate cancer xenografts both radionuclides seemed to be equally effective after prostate-specific antigen promoter-mediated NIS gene delivery, a superior therapeutic effect has been demonstrated for 188Re in larger tumors.

scholarly journals Telomerase-Driven Expression of the Sodium Iodide Symporter (NIS) for in Vivo Radioiodide Treatment of Cancer: A New Broad-Spectrum NIS-Mediated Antitumor Approach

2011 ◽  
Vol 96 (9) ◽  
pp. E1435-E1443 ◽  
Author(s):  
Garcilaso Riesco-Eizaguirre ◽  
Antonio De la Vieja ◽  
Irene Rodríguez ◽  
Soledad Miranda ◽  
Pilar Martín-Duque ◽  
...  
Keyword(s):  
Therapeutic Effect ◽  
Cell Lines ◽  
Sodium Iodide ◽  
Human Cancer ◽  
131I Therapy ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Tumor Xenografts ◽  
Human Cancer Cell Lines

Abstract Context: Telomerase promoters (hTERT and hTR) are useful for transcriptional targeting in gene therapy models of cancer. Telomerase-driven expression of the sodium iodide symporter (NIS) in tumor cells has been successfully used as a reporter gene in vivo using positron emission tomography (PET) imaging. Objective: The aim of this study was to investigate the NIS-mediated therapeutic effect of telomerase promoters in a wide variety of human cancer cell lines. Design and Methods: Promoter fragments from either hTERT or hTR were used to drive the expression of NIS in cell lines derived from melanoma (M14), breast (MDA-MB-231), colon (HT-29), lung (H460), ovarian (OVCAR-3), and thyroid (TPC-1) carcinomas. Iodide uptake assays, protein immunodetection, and clonigenic assays were used to confirm NIS functional expression and the 131I-mediated cytopathic effect. Tumor xenografts in mice were infected with hTERT and hTR and then treated using radioiodide. Results: Both promoters were selectively active in cancer cells that were effectively killed by exposure to 131I. One single dose of 1 mCi 131I markedly suppressed tumor growth of melanoma-derived tumor xenografts compared with controls. This effect was more modest in colon cancer-derived xenografts in part due to the reduced infectivity and the tumor cystic nature. The therapeutic effect of hTR promoter was found to be stronger than that of hTERT promoter. Conclusions: These results demonstrate that telomerase-driven expression of NIS could potentially have applications for 131I therapy of a wide variety of cancers. Additionally, this is the first study to report NIS-mediated 131I therapy of melanoma tumors in vivo.

Systemic tumor-targeted sodium iodide symporter (NIS) gene therapy of hepatocellular carcinoma mediated by B6 peptide polyplexes

2017 ◽  
Vol 19 (5) ◽  
pp. e2957 ◽  
Author(s):  
Sarah Urnauer ◽  
Kathrin Klutz ◽  
Geoffrey K. Grünwald ◽  
Stephan Morys ◽  
Nathalie Schwenk ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gene Therapy ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Nis Gene
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