Noninvasive radiological imaging of pulmonary gene transfer and expression using the human sodium iodide symporter

Gang Niu; Kimberly J Krager; Michael M Graham; Richard D Hichwa; Frederick E Domann

doi:10.1007/s00259-004-1715-6

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Noninvasive radiological imaging of pulmonary gene transfer and expression using the human sodium iodide symporter

Journal article

Peer reviewed

Noninvasive radiological imaging of pulmonary gene transfer and expression using the human sodium iodide symporter

Gang Niu, Kimberly J Krager, Michael M Graham, Richard D Hichwa and Frederick E Domann

European journal of nuclear medicine and molecular imaging, Vol.32(5), pp.534-540

05/2005

DOI: 10.1007/s00259-004-1715-6

PMID: 15599523

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Abstract

In this study we investigated the application of the human sodium iodide symporter (hNIS) as a reporter gene to noninvasively image in vivo gene transfer and expression in lung tissue in real time. Human NIS-expressing adenoviruses (Ad-hNIS) or empty adenoviruses (Ad-Bgl II) were instilled into the lungs of Cotton rats via the nostrils. After 3, 10, and 17 days post infection, gamma camera scintigraphy with 99mTcO4- was performed to observe the distribution and duration of gene transfer. At 20 days after infection, reverse transcription polymerase chain reaction was performed to detect hNIS gene expression. Dual expressing vector Ad-hNIS-eGFP was used to detect transgene expression by fluorescence photomicroscopy in infected lung tissue. Positron emission tomography (PET) imaging of gene transfer to the lungs was performed using 124I- as tracer. Finally, hNIS transfer to a polarized human airway epithelial cell layer was evaluated by phosphorimaging. Lungs in animals infected with Ad-hNIS were clearly visible on scintigraphy and PET scans, while those infected with Ad-Bgl II were undetectable. Lungs in Ad-hNIS infected animals could still be visualized at 17 days but were no longer detectable at 20 days. Fluorescence microscopy showed that lung tissue infected with Ad-hNIS-eGFP had significantly higher GFP signal intensity than that infected with Ad-Bgl II. It is feasible to use the hNIS gene as a reporter gene to monitor the location, magnitude, and timing of expression of genes delivered during pulmonary gene therapy. The ability to noninvasively visualize gene expression tomographically in real time has significant translational implications in human gene therapy.

Gene Transfer Techniques

Molecular Probe Techniques

Humans

Gene Expression Regulation - physiology

Rats

Gene Expression Profiling - methods

Lung - diagnostic imaging

Positron-Emission Tomography - methods

Symporters - metabolism

Feasibility Studies

Sigmodontinae

Animals

Transfection - methods

Symporters - genetics

Lung - metabolism

Genes, Reporter

Details

Title: Subtitle: Noninvasive radiological imaging of pulmonary gene transfer and expression using the human sodium iodide symporter
Creators: Gang Niu - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, B 180 Med Labs, Iowa City, IA 52242, USA
Kimberly J Krager
Michael M Graham
Richard D Hichwa
Frederick E Domann
Resource Type: Journal article
Publication Details: European journal of nuclear medicine and molecular imaging, Vol.32(5), pp.534-540
Publisher: Germany
DOI: 10.1007/s00259-004-1715-6
PMID: 15599523
ISSN: 1619-7070
eISSN: 1619-7089
Grant note: NIH CA91709 / NCI NIH HHS
Language: English
Date published: 05/2005
Academic Unit: Radiology; Research Administration; Pathology; Surgery; Physics and Astronomy; Radiation Oncology
Record Identifier: 9984047684602771

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