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Imaging the spatial distribution of transgene expression in the lungs with positron emission tomography

Gene Therapy volume 10, pages 2074–2080 (2003)Cite this article

Abstract

This study was designed to evaluate the utility of positron emission tomography (PET) to quantify the magnitude and spatial distribution of transgene expression after different methods of adenoviral vector delivery (with surfactant- and saline-based vehicles) within rat lungs. In all, 17 animals (eight in the surfactant group, nine in the saline group) were studied 3 days after intratracheal administration of a replication-incompetent adenovirus encoding a mutant Herpes simplex virus-1 thymidine kinase (mHSV1-TK)-enhanced green fluorescent protein fusion gene driven by a Cytomegalovirus promoter (Ad-CMV-mNLS-HSV1sr39tk-egfp). PET images were obtained 1 h after i.v. administration of 9-(4-[18F]-fluoro-3-hydroxymethylbutyl)guanine ([18F]-FHBG), an imaging substrate for mHSV1-TK. Overall, the average lung concentration of [18F]-FHBG was significantly greater in the surfactant group than in the saline group (0.24±0.06 versus 0.17±0.03% injected dose/ml lung, P⩽0.05). Lung [18F]-FHBG distribution was more peripheral and more homogeneous in the surfactant group than in the saline group (mean coefficient of variation=31±4 versus 36±3%, respectively, P⩽0.05). Regions of increased tracer concentration in the surfactant group compared to the saline group were evenly distributed throughout the lungs. We conclude that PET imaging provides useful and meaningful information about the effectiveness of different gene transfer delivery strategies within the lungs, and that surfactant-based vehicles may be a superior strategy for pulmonary gene transfer.

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Acknowledgements

We thank Jim Kozlowski for his contribution to this study, Datta Ponde and Carmen Dence for radiopharmaceutical production, and gratefully acknowledge the support provided by the microPET facility staff in the Division of Radiological Sciences of Washington University School of Medicine. The work was funded by NIH HL32815, HL13851, HL66211 and the Evanston Northwestern Healthcare Research Institute.

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Authors and Affiliations

  1. Washington University School of Medicine, St Louis, MO, USA

    J-C Richard & D P Schuster

  2. Columbia University College of Physicians and Surgeons, New York, NY, USA

    P Factor

  3. Evanston Northwestern Healthcare, Evanston, IL, USA

    L C Welch

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  1. J-C Richard
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  4. D P Schuster
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Richard, JC., Factor, P., Welch, L. et al. Imaging the spatial distribution of transgene expression in the lungs with positron emission tomography. Gene Ther 10, 2074–2080 (2003). https://doi.org/10.1038/sj.gt.3302117

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