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Direct correlation between positron emission tomographic images of two reporter genes delivered by two distinct adenoviral vectors

Gene Therapy volume 8, pages 1072–1080 (2001)Cite this article

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 (D2R), 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-D2R express both reporter genes with good correlation (r2 = 0.93). Similarly, a high correlation (r2 = 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 D2R expression with 9-(4-[18F]fluoro-3-hydroxymethylbutyl) guanine ([18F]FHBG) and 3-(2-[18F]fluoroethyl)spiperone ([18F]FESP), utilizing several adenovirus-mediated delivery routes, illustrates the feasibility of evaluating relative levels of transgene expression in living animals, using this approach.

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Acknowledgements

We thank the members of the UCLA Gene Imaging Consortium, K Nguyen, E Bauer and Y Yu for various technical assistance, R Sumida, W Ladno, J Edwards, DJ Liu and V Dominguez for assistance with microPET imaging, M Ho for the synthesis of [18F]FESP and [18F]FHBG and the UCLA cyclotron crew for outstanding support. We are grateful for J Matherly's assistance with adenovirus replication. We thank A Green for helpful discussions. Grants: this work was partially supported by funding from NIH RO1 CA82214–01, DOE contract DE-FC03–87ER60615, University of California Biotechnology Grant, Dana Foundation, and the UCLA-Jonsson Comprehensive Cancer Center.

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Authors and Affiliations

  1. Department of Molecular and Medical Pharmacology, The Division of Nuclear Medicine, UCLA School of Medicine, Los Angeles, CA, USA

    SS Yaghoubi, T Toyokuni, JR Barrio, M Namavari, N Satyamurthy, ME Phelps, HR Herschman & SS Gambhir

  2. The Crump Institute for Biological Imaging, UCLA School of Medicine, Los Angeles, CA, USA

    SS Yaghoubi, T Toyokuni, ME Phelps, HR Herschman & SS Gambhir

  3. UCLA/DOE Laboratory of Structural Biology and Molecular Medicine, UCLA School of Medicine, Los Angeles, CA, USA

    T Toyokuni, JR Barrio, M Namavari, N Satyamurthy, ME Phelps, HR Herschman & SS Gambhir

  4. Molecular Biology Institute, UCLA School of Medicine, Los Angeles, CA, USA

    L Wu, Q Liang & HR Herschman

  5. Department of Biomathematics, UCLA School of Medicine, Los Angeles, CA, USA

    ME Phelps & SS Gambhir

  6. UCLA-Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, CA, USA

    L Wu, HR Herschman & SS Gambhir

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  1. SS Yaghoubi
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Yaghoubi, S., Wu, L., Liang, Q. et al. Direct correlation between positron emission tomographic images of two reporter genes delivered by two distinct adenoviral vectors. Gene Ther 8, 1072–1080 (2001). https://doi.org/10.1038/sj.gt.3301490

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  • DOI: https://doi.org/10.1038/sj.gt.3301490

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