Title |
Angiotensin II increases gene expression after selective intra-arterial adenovirus delivery in a rabbit model assessed using in vivo SSTR2-based reporter imaging
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Published in |
EJNMMI Research, March 2016
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DOI | 10.1186/s13550-016-0183-x |
Pubmed ID | |
Authors |
Sheela P. Singh, Murali K. Ravoori, Katherine A. Dixon, Lin Han, Sanjay Gupta, Rajesh Uthamanthil, Kenneth C. Wright, Vikas Kundra |
Abstract |
Gene therapy has been hampered by low expression upon in vivo delivery. Using a somatostatin receptor type 2 (SSTR2)-based reporter, we assessed whether angiotensin II (AII) can improve gene expression by adenovirus upon intra-arterial (IA) delivery in a large animal model. A SSTR2-based reporter that can be imaged by a clinically approved radiopharmaceutical was used to assess gene expression. Eight rabbits bearing VX2 tumors in each thigh were randomly injected IA with adenovirus containing a human SSTR2 (Ad-CMV-HA-SSTR2) gene chimera ± AII or control adenovirus containing green fluorescent protein (Ad-CMV-GFP). Three days later, (111)In-octreotide was given IV after computed tomography (CT) imaging using a clinical CT scanner and intravenous contrast. Tumor uptake of (111)In-octreotide was evaluated the next day using a clinical gamma camera. Gene expression was normalized to tumor weight and morphology from CT to obtain in vivo biodistribution. SSTR2-based expression was readily visualized. VX2 tumors infected with Ad-CMV-HA-SSTR2 upon intra-arterial delivery with AII had greater in vivo biodistribution, thus greater gene expression, than those without AII (p < 0.01, n = 6). VX2 tumors infected with Ad-CMV-HA-SSTR2 upon IA delivery had greater biodistribution, thus greater gene expression, than those with the negative control Ad-CMV-GFP (p < 0.02). Similarly, VX2 tumors infected with Ad-CMV-HA-SSTR2 upon IA delivery with AII had greater biodistribution, thus greater gene expression, than those with the negative control Ad-CMV-GFP (p < 0.01). Angiotensin II improves in vivo gene expression by adenovirus upon intra-arterial delivery and thus may improve gene therapy efficacy. In vivo SSTR2-based reporter imaging can be used to compare methodologies for improving gene expression. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 73 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 6 | 8% |
Student > Master | 6 | 8% |
Researcher | 5 | 7% |
Student > Postgraduate | 4 | 5% |
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Unknown | 19 | 26% |
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Biochemistry, Genetics and Molecular Biology | 3 | 4% |
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