Angiotensin II increases gene expression after selective intra-arterial adenovirus delivery in a rabbit model assessed using in vivo SSTR2-based reporter imaging

Background 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. Methods 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. Results 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