SPECT/CT imaging of oncolytic adenovirus propagation in tumours in vivo using the Na/I symporter as a reporter gene.
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
Merron
A
A
Centre for Molecular Oncology, Institute of Cancer, Queen Mary's School of Medicine and Dentistry, London, UK.
Peerlinck
I
I
Martin-Duque
P
P
Burnet
J
J
Quintanilla
M
M
Mather
S
S
Hingorani
M
M
Harrington
K
K
Iggo
R
R
Vassaux
G
G
D000256:Adenoviridae / Q000235:genetics; D000257:Adenoviridae Infections / Q000000981:diagnostic imaging; D000818:Animals; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000628:therapy* / Q000821:virology; D015870:Gene Expression; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D015552:Injections, Intralesional; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D050130:Oncolytic Virotherapy / Q000379:methods*; D027981:Symporters / Q000235:genetics*; D015899:Tomography, Emission-Computed, Single-Photon; D014161:Transduction, Genetic / Q000379:methods; D014183:Transplantation, Heterologous; D014779:Virus Replication; D000099209:Sodium-Iodide Symporters
D027981:Symporters; D000099209:Sodium-Iodide Symporters