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Direct correlation between positron emission tomographic images of two reporter genes delivered by two distinct adenoviral vectors
- Source :
- Gene Therapy. 8:1072-1080
- Publication Year :
- 2001
- Publisher :
- Springer Science and Business Media LLC, 2001.
-
Abstract
- Biodistribution, magnitude and duration of a therapeutic transgene's expression may be assessed by linking it to the expression of a positron emission tomography (PET) reporter gene (PRG) and then imaging the PRG's expression by a PET reporter probe (PRP) in living animals. We validate the simple approach of co-administering two distinct but otherwise identical adenoviruses, one expressing a therapeutic transgene and the other expressing the PRG, to track the therapeutic gene's expression. Two PET reporter genes, a mutant herpes simplex virus type 1 thymidine kinase (HSV1-sr39tk) and dopamine-2 receptor (D(2)R), each regulated by the same cytomegalovirus (CMV) promoter, have been inserted into separate adenoviral vectors (Ad). We demonstrate that cells co-infected with equivalent titers of Ad-CMV-HSV1-sr39tk and Ad-CMV-D(2)R express both reporter genes with good correlation (r(2) = 0.93). Similarly, a high correlation (r(2) = 0.97) was observed between the expression of both PRGs in the livers of mice co-infected via tail-vein injection with equivalent titers of these two adenoviruses. Finally, microPET imaging of HSV1-sr39tk and D(2)R expression with 9-(4-[(18)F]fluoro-3-hydroxymethylbutyl) guanine ([(18)F]FHBG) and 3-(2-[(18)F]fluoroethyl)spiperone ([(18)F]FESP), utilizing several adenovirus-mediated delivery routes, illustrates the feasibility of evaluating relative levels of transgene expression in living animals, using this approach.
- Subjects :
- Biodistribution
Guanine
Time Factors
Transgene
Genetic enhancement
Genetic Vectors
Cytomegalovirus
Gene Expression
Mice, Nude
Mice, Inbred Strains
Herpesvirus 1, Human
Biology
medicine.disease_cause
Thymidine Kinase
Adenoviridae
Mice
Gene expression
Genetics
medicine
Animals
Promoter Regions, Genetic
Molecular Biology
Cells, Cultured
Reporter gene
Receptors, Dopamine D2
Molecular biology
Rats
Herpes simplex virus
Liver
Spiperone
Thymidine kinase
COS Cells
Feasibility Studies
Molecular Medicine
Tomography, Emission-Computed
Subjects
Details
- ISSN :
- 14765462 and 09697128
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Gene Therapy
- Accession number :
- edsair.doi.dedup.....f4a5618158ffed5b7433d4b9ad0bc6ad
- Full Text :
- https://doi.org/10.1038/sj.gt.3301490