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Title: Preliminary validation of varicella zoster virus thymidine kinase as a novel reporter gene for PET
Authors: Deroose, Christophe
Chitneni, Satish K
Gijsbers, Rik
Vermaelen, Peter
Ibrahimi, Abdelilah
Balzarini, Jan
Baekelandt, Veerle
Verbruggen, Alfons
Nuyts, Johan
Debyser, Zeger
Bormans, Guy
Mortelmans, Luc # ×
Issue Date: Nov-2012
Publisher: Pergamon Press
Series Title: Nuclear Medicine and Biology vol:39 issue:8 pages:1266-1274
Article number: S0969-8051(12)00191-6
Abstract: INTRODUCTION: Imaging of gene expression with positron emission tomography (PET) has emerged as a powerful tool for biomedical research during the last decade. The prototypical herpes simplex virus type 1 thymidine kinase (HSV1-TK) PET reporter gene (PRG) is widely used and many other PRGs have also been validated. We investigated varicella zoster virus thymidine kinase (VZV-tk) as new PRG with radiolabeled bicyclic nucleoside analogues (BCNAs) as PET tracers. METHODS: The uptake and washout of four different radiolabeled BCNAs was evaluated in cells expressing VZV-tk after lentiviral vector (LV) transduction and in control cells. Metabolism of the tracers was assayed by high pressure liquid chromatography (HPLC). Mice bearing VZV-TK expressing xenografts were imaged with PET. RESULTS: High uptake in VZV-tk expressing cells was seen for 3 of the 4 tracers tested. The uptake of the tracers could be blocked by the presence of excess thymidine in the incubation solution. Cellular retention was variable, with one tracer showing an acceptable half-life of ~1 hour. The amount of intracellular tracer correlated with the titer of LV used to transduce the cells. VZV-TK dependent conversion into metabolites was shown by HPLC. No specific accumulation was observed in cells expressing a fusion protein containing an HSV1-TK moiety. VZV-tk expression in xenografts resulted in a 60% increase in uptake in vivo as measured with PET. CONCLUSIONS: We have validated the combination of VZV-tk and radiolabeled BCNAs as new PRG/PRP system. Further optimization of the PRPs and the PRG are warranted to increase the signal.
URI: 
ISSN: 0969-8051
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
Molecular Virology and Gene Therapy
Radiopharmacy
Nuclear Medicine & Molecular Imaging
Research Group for Neurobiology and Gene Therapy
× corresponding author
# (joint) last author

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