The use of high-frequency ultrasound imaging and biofluorescence for in vivo evaluation of gene therapy vectors.
BACKGROUND
Non-invasive imaging of the biodistribution of novel therapeutics including gene therapy vectors in animal models is essential.


METHODS
This study assessed the utility of high-frequency ultrasound (HF-US) combined with biofluoresence imaging (BFI) to determine the longitudinal impact of a Herpesvirus saimiri amplicon on human colorectal cancer xenograft growth.


RESULTS
HF-US imaging of xenografts resulted in an accurate and informative xenograft volume in a longitudinal study. The volumes correlated better with final ex vivo volume than mechanical callipers (R2 = 0.7993, p = 0.0002 vs. R2 = 0.7867, p = 0.0014). HF-US showed that the amplicon caused lobe formation. BFI demonstrated retention and expression of the amplicon in the xenografts and quantitation of the fluorescence levels also correlated with tumour volumes.


CONCLUSIONS
The use of multi-modal imaging provided useful and enhanced insights into the behaviour of gene therapy vectors in vivo in real-time. These relatively inexpensive technologies are easy to incorporate into pre-clinical studies.
School of Medicine, University of Leeds Brenner Building, St James's University Hospital, Leeds LS9 7TF, UK. n.ingram@leeds.ac.uk.
Nicola
N
Ingram
Stuart A
SA
Macnab
Gemma
G
Marston
Nigel
N
Scott
Ian M
IM
Carr
Alexander F
AF
Markham
Adrian
A
Whitehouse
P Louise
PL
Coletta
D000818:Animals; D015179:Colorectal Neoplasms / Q000473:pathology* / Q000628:therapy*; D015316:Genetic Therapy; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D045325:HCT116 Cells; D006567:Herpesvirus 2, Saimiriine / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D051379:Mice; D008819:Mice, Nude; D064847:Multimodal Imaging; D061848:Optical Imaging / Q000379:methods*; D047368:Tumor Burden; D014463:Ultrasonography / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
D049452:Green Fluorescent Proteins