SPECT/CT imaging of oncolytic adenovirus propagation in tumours in vivo using the Na/I symporter as a reporter gene.
Date
2007-12ICR Author
Author
Merron, A
Peerlinck, I
Martin-Duque, P
Burnet, J
Quintanilla, M
Mather, S
Hingorani, M
Harrington, K
Iggo, R
Vassaux, G
Type
Journal Article
Metadata
Show full item recordAbstract
Oncolytic adenoviruses have shown some promise in cancer gene therapy. However, their efficacy in clinical trials is often limited, and additional therapeutic interventions have been proposed to increase their efficacies. In this context, molecular imaging of viral spread in tumours could provide unique information to rationalize the timing of these combinations. Here, we use the human sodium iodide symporter (hNIS) as a reporter gene in wild-type and replication-selective adenoviruses. By design, hNIS cDNA is positioned in the E3 region in a wild-type adenovirus type 5 (AdIP1) and in an adenovirus in which a promoter from the human telomerase gene (RNA component) drives E1 expression (AdAM6). Viruses show functional hNIS expression and replication in vitro and kinetics of spread of the different viruses in tumour xenografts are visualized in vivo using a small animal nano-SPECT/CT camera. The time required to reach maximal spread is 48 h for AdIP1 and 72 h for AdAM6 suggesting that genetic engineering of adenoviruses can affect their kinetics of spread in tumours. Considering that this methodology is potentially clinically applicable, we conclude that hNIS-mediated imaging of viral spread in tumours may be an important tool for combined anticancer therapies involving replicating adenoviruses
Collections
Subject
Animals
Mice, Inbred BALB C
Humans
Mice
Adenoviridae
Adenoviridae Infections
Colonic Neoplasms
Symporters
Tomography, Emission-Computed, Single-Photon
Transplantation, Heterologous
Injections, Intralesional
Transduction, Genetic
Neoplasm Transplantation
Virus Replication
Gene Expression
Genes, Reporter
Oncolytic Virotherapy
Genetic Therapy
Research team
Targeted Therapy
Language
eng
License start date
2007-12
Citation
Gene therapy, 2007, 14 (24), pp. 1731 - 1738