title: Angiotensin II increases gene expression after selective intra-arterial adenovirus delivery in a rabbit model assessed using in vivo SSTR2-based reporter imaging.
abstract: 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 < 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
authors.forename: Sheela P
authors.initials: SP
authors.lastname: Singh
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
authors.forename: Murali K
authors.initials: MK
authors.lastname: Ravoori
authors.affiliation: Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Dixon
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Uthamanthil
authors.affiliation: Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Wright
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. vkundra@mdanderson.org.|Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. vkundra@mdanderson.org.|UT MD Anderson Cancer Center, 1400 Pressler St., Unit 1473, Houston, TX, 77030, USA. vkundra@mdanderson.org.
authors.forename: Vikas
authors.initials: V
authors.lastname: Kundra
keywords: Angiotensin II; Gene delivery; Gene therapy; Imaging; Somatostatin receptor type 2