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PET imaging of thymidine kinase gene expression in the liver of non-human primates following systemic delivery of an adenoviral vector
Authors: Fontanellas, A. (Antonio)
Hervas-Stubbs, S. (Sandra)
Sampedro, A. (Ana)
Collantes, M. (María)
Azpilicueta, A. (Arantza)
Mauleon, I. (Itsaso)
Pañeda, A. (Astrid)
Quincoces, G. (Gemma)
Prieto, J. (Jesús)
Melero, I. (Ignacio)
Peñuelas, I. (Iván)
Keywords: PET
Thymidine kinase
Issue Date: 30-Jun-2008
Publisher: Nature Publishing Group
Publisher version:
ISSN: 0969-7128
Citation: Fontanellas A, Hervas-Stubbs S, Sampedro A, Collantes M, Azpilicueta A, Mauleon I, et al. PET imaging of thymidine kinase gene expression in the liver of non-human primates following systemic delivery of an adenoviral vector. Gene Ther 2009 Jan;16(1):136-141.
Non-invasive in vivo imaging of transgene expression is currently providing very important means to optimize gene therapy regimes. Results in non-human primates are considered the most predictive models for the outcome in patients. In this study, we have documented that tumour and primary cell lines from human and non-human primates are comparably gene-transduced in vitro by serotype 5 adenovirus expressing HSV1-thymidine kinase. Transgene expression can be quantified in human and monkey cultured cells by positron emission tomography (PET) imaging when transduced cells are incubated with a fluoride-18 labelled penciclovir analogue. In our hands, PET images of cell cultures estimate the number of transduced cells rather than intensity of transgene expression once a threshold of TK per cell is reached. Interestingly, in vivo systemic administration of a clinical grade recombinant adenovirus expressing TK into macaques gives rise to an intense retention of the radiotracer in the liver parenchyma, providing an experimental system to visualize transgene expression that ought to be similar in human and macaques. Such imaging methodology might contribute to improve strategies based on adenoviral vectors.
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Appears in Collections:DA - CIMA - Servicios de apoyo - Micropet - Artículos de revista
DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología terapia génica - Artículos de revista
DA - Ciencias - HAP - Artículos de revista

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