Imaging pulmonary gene expression with positron emission tomography

Jean Cristophe Richard, Zhaohui Zhou, Datta E. Ponde, Carmen S. Dence, Philip Factor, Paul N. Reynolds, Gary D. Luker, Vijay Sharma, Tom Ferkol, David Piwnica-Worms, Daniel P. Schuster

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

We evaluated positron emission tomographic imaging of pulmonary transgene expression, using an enhanced mutant herpes simplex virus-1 thymidine kinase as the reporter gene, in the lungs of normal rats. Sixteen rats were studied 3 days after an intratracheal administration of 5 × 109 to 1 × 1011 viral particles of a replication-incompetent adenovirus containing a fusion gene of the mutant kinase and green fluorescent protein. Three rats infected with adenovirus containing no insert (null vector) served as control subjects. Images were obtained 1 hour after an intravenous injection of 9-(4-[18F]-fluoro-3-hydroxymethylbutyl)guanine, an imaging substrate for the viral kinase. After euthanasia, tissue radioactivity was determined in a γ counter, and thymidine kinase activity and green fluorescent protein levels were measured in lung tissue samples. Imaging and γ counting radioactivity measurements were strongly and linearly correlated (r2 = 0.96, p < 0.001). Imaging detected thymidine kinase expression above background (null vector) in 15 of 16 rats, even at low viral doses that produced little to no measurable green fluorescent protein expression. Lung 9-(4-[18F]-fluoro-3-hydroxymethylbutyl)guanine uptake (as assessed by imaging) correlated with in vitro assays of both kinase activity (r2 = 0.48, p < 0.001) and fluorescent protein (r2 = 0.46, p < 0.001). We conclude that positron emission tomographic imaging is a sensitive and quantitative method for detecting pulmonary reporter gene expression noninvasively.

Original languageEnglish
Pages (from-to)1257-1263
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Volume167
Issue number9
DOIs
StatePublished - May 1 2003

Keywords

  • Green fluorescent protein
  • Positron emission tomography
  • Rats
  • Reporter gene

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