Somatostatin Receptor Type 2–Based Reporter Expression after Plasmid-Based in Vivo Gene Delivery to Non–Small Cell Lung Cancer
Plasmids tend to have much lower expression than viruses. Gene expression after systemic administration of plasmid vectors has not been assessed using somatostatin receptor type 2 ( SSTR2 )-based reporters. The purpose of this work was to identify gene expression in non–small cell lung cancer (NSCLC...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publications
2013-10-01
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| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.2310/7290.2013.00060 |
| _version_ | 1797283603603783680 |
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| author | Lin Han Murali Ravoori Guanglin Wu Ryo Sakai Shaoyu Yan Sheela Singh Kai Xu Jack A. Roth Lin Ji Vikas Kundra |
| author_facet | Lin Han Murali Ravoori Guanglin Wu Ryo Sakai Shaoyu Yan Sheela Singh Kai Xu Jack A. Roth Lin Ji Vikas Kundra |
| author_sort | Lin Han |
| collection | DOAJ |
| description | Plasmids tend to have much lower expression than viruses. Gene expression after systemic administration of plasmid vectors has not been assessed using somatostatin receptor type 2 ( SSTR2 )-based reporters. The purpose of this work was to identify gene expression in non–small cell lung cancer (NSCLC) after systemic liposomal nanoparticle delivery of plasmid containing SSTR2-based reporter gene. In vitro, Western blotting was performed after transient transfection with the plasmid cytomegalovirus (CMV)-SSTR2, CMV-TUSC2-IRES-SSTR2, or CMV-TUSC2. SSTR2 is the reporter gene, and TUSC2 is a therapeutic gene. Mice with A549 NSCLC lung tumors were injected intravenously with CMV-SSTR2, CMV-TUSC2-IRES-SSTR2, or CMV-TUSC2 plasmids in DOTAP:cholesterolliposomal nanoparticles. Two days later, mice were injected intravenously with 111 In-octreotide. The next day, biodistribution was performed. The experiment was repeated including single-photon emission computed tomography/computed tomography (SPECT/CT). Immunohistochemistry was performed. In vitro, SSTR2 expression was similar in cells transfected with CMV-SSTR2 or CMV-TUSC2-IRES-SSTR2. TUSC2 expression was similar in cells transfected with CMV-TUSC2 or CMV-TUSC2-SSTR2. Biodistribution demonstrated significantly greater 111 In-octreotide uptake in tumors from mice injected with CMV-TUSC2-IRES-SSTR2 or CMV-SSTR2 than the control plasmid, CMV-TUSC2 ( p < .05). Gamma-camera and SPECT/CT imaging illustrated SSTR2 expression in tumors in mice injected with CMV-TUSC2-IRES-SSTR2 or CMV-SSTR2 versus background with control plasmid. Immunohistochemistry corresponded with imaging. SSTR2-based reporter imaging can visualize gene expression in lung tumors after systemic liposomal nanoparticle delivery of plasmid containing SSTR2-based reporter gene or SSTR2 linked to a second therapeutic gene, such as TUSC2 . |
| first_indexed | 2024-03-07T17:34:11Z |
| format | Article |
| id | doaj.art-79e5e7e427a5441caf226813496fabb9 |
| institution | Directory Open Access Journal |
| issn | 1536-0121 |
| language | English |
| last_indexed | 2024-03-07T17:34:11Z |
| publishDate | 2013-10-01 |
| publisher | SAGE Publications |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj.art-79e5e7e427a5441caf226813496fabb92024-03-02T17:13:35ZengSAGE PublicationsMolecular Imaging1536-01212013-10-011210.2310/7290.2013.0006010.2310_7290.2013.00060Somatostatin Receptor Type 2–Based Reporter Expression after Plasmid-Based in Vivo Gene Delivery to Non–Small Cell Lung CancerLin HanMurali RavooriGuanglin WuRyo SakaiShaoyu YanSheela SinghKai XuJack A. RothLin JiVikas KundraPlasmids tend to have much lower expression than viruses. Gene expression after systemic administration of plasmid vectors has not been assessed using somatostatin receptor type 2 ( SSTR2 )-based reporters. The purpose of this work was to identify gene expression in non–small cell lung cancer (NSCLC) after systemic liposomal nanoparticle delivery of plasmid containing SSTR2-based reporter gene. In vitro, Western blotting was performed after transient transfection with the plasmid cytomegalovirus (CMV)-SSTR2, CMV-TUSC2-IRES-SSTR2, or CMV-TUSC2. SSTR2 is the reporter gene, and TUSC2 is a therapeutic gene. Mice with A549 NSCLC lung tumors were injected intravenously with CMV-SSTR2, CMV-TUSC2-IRES-SSTR2, or CMV-TUSC2 plasmids in DOTAP:cholesterolliposomal nanoparticles. Two days later, mice were injected intravenously with 111 In-octreotide. The next day, biodistribution was performed. The experiment was repeated including single-photon emission computed tomography/computed tomography (SPECT/CT). Immunohistochemistry was performed. In vitro, SSTR2 expression was similar in cells transfected with CMV-SSTR2 or CMV-TUSC2-IRES-SSTR2. TUSC2 expression was similar in cells transfected with CMV-TUSC2 or CMV-TUSC2-SSTR2. Biodistribution demonstrated significantly greater 111 In-octreotide uptake in tumors from mice injected with CMV-TUSC2-IRES-SSTR2 or CMV-SSTR2 than the control plasmid, CMV-TUSC2 ( p < .05). Gamma-camera and SPECT/CT imaging illustrated SSTR2 expression in tumors in mice injected with CMV-TUSC2-IRES-SSTR2 or CMV-SSTR2 versus background with control plasmid. Immunohistochemistry corresponded with imaging. SSTR2-based reporter imaging can visualize gene expression in lung tumors after systemic liposomal nanoparticle delivery of plasmid containing SSTR2-based reporter gene or SSTR2 linked to a second therapeutic gene, such as TUSC2 .https://doi.org/10.2310/7290.2013.00060 |
| spellingShingle | Lin Han Murali Ravoori Guanglin Wu Ryo Sakai Shaoyu Yan Sheela Singh Kai Xu Jack A. Roth Lin Ji Vikas Kundra Somatostatin Receptor Type 2–Based Reporter Expression after Plasmid-Based in Vivo Gene Delivery to Non–Small Cell Lung Cancer Molecular Imaging |
| title | Somatostatin Receptor Type 2–Based Reporter Expression after Plasmid-Based in Vivo Gene Delivery to Non–Small Cell Lung Cancer |
| title_full | Somatostatin Receptor Type 2–Based Reporter Expression after Plasmid-Based in Vivo Gene Delivery to Non–Small Cell Lung Cancer |
| title_fullStr | Somatostatin Receptor Type 2–Based Reporter Expression after Plasmid-Based in Vivo Gene Delivery to Non–Small Cell Lung Cancer |
| title_full_unstemmed | Somatostatin Receptor Type 2–Based Reporter Expression after Plasmid-Based in Vivo Gene Delivery to Non–Small Cell Lung Cancer |
| title_short | Somatostatin Receptor Type 2–Based Reporter Expression after Plasmid-Based in Vivo Gene Delivery to Non–Small Cell Lung Cancer |
| title_sort | somatostatin receptor type 2 based reporter expression after plasmid based in vivo gene delivery to non small cell lung cancer |
| url | https://doi.org/10.2310/7290.2013.00060 |
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