title: Somatostatin receptor type 2-based reporter expression after plasmid-based in vivo gene delivery to non-small cell lung cancer.
abstract: 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:cholesterol-liposomal nanoparticles. Two days later, mice were injected intravenously with 111In-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 111In-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.
authors: Lin
authors: L
authors: Han
authors: Murali
authors: M
authors: Ravoori
authors: Guanglin
authors: G
authors: Wu
authors: Ryo
authors: R
authors: Sakai
authors: Shaoyu
authors: S
authors: Yan
authors: Sheela
authors: S
authors: Singh
authors: Kai
authors: K
authors: Xu
authors: Jack A
authors: JA
authors: Roth
authors: Lin
authors: L
authors: Ji
authors: Vikas
authors: V
authors: Kundra
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D003587:Cytomegalovirus / Q000235:genetics; D005260:Female; D017930:Genes, Reporter; D015316:Genetic Therapy; D005822:Genetic Vectors; D064593:Heterografts; D006801:Humans; D007205:Indium Radioisotopes; D008081:Liposomes; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D015282:Octreotide / Q000031:analogs & derivatives; D010957:Plasmids; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin / Q000235:genetics* / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D007205:Indium Radioisotopes; D008081:Liposomes; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; C499993:TUSC2 protein, human; D025521:Tumor Suppressor Proteins; C094279:indium-111-octreotide; C093733:somatostatin receptor 2; D015282:Octreotide
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