In vivo molecular imaging characterizes pulmonary gene expression in experimental lung transplantation
Introduction: Gene therapy is effective in preventing ischemia-reperfusion injury and allograft rejection after experimental lung transplantation. Currently, no means exist to noninvasively determine the distribution, magnitude and timing of transgene expression after transplantation. This study uti...
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Published in | Journal of the American College of Surgeons Vol. 199; no. 3; pp. 32 - 33 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Elsevier Inc
01.09.2004
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Abstract | Introduction: Gene therapy is effective in preventing ischemia-reperfusion injury and allograft rejection after experimental lung transplantation. Currently, no means exist to noninvasively determine the distribution, magnitude and timing of transgene expression after transplantation. This study utilizes a novel PET reporter gene system to characterize transgene expression after experimental lung transplantation.
Methods: Experiments utilized a rodent orthotopic left lung transplant model. Donors underwent endotracheal transfection 24 hours before harvest with 5x1010 VPs of adenovirus encoding a fusion gene of thymidine kinase (TK, PET reporter gene) and green fluorescent protein. PET images were obtained in 4 groups of recipients: 24 hours postoperatively with and without I/R injury, and 4 days postoperatively with and without acute rejection. Rats which underwent transfection alone served as controls. Excised lungs were assessed for gamma counter radioactivity and TK activity.
Results: Transplanted lungs displayed strong and linear correlation between PET signals and gamma counter radioactivity (r2 = 0.82, p < 0.01). PET imaging also correlated with tissue TK activity (r2 = 0.44, p < 0.01). There was no difference in apparent lung volumes by PET between transplanted lungs with and without I/R injury and rejection.
Conclusions: PET imaging is a sensitive and quantitative method for characterizing pulmonary transgene expression in experimental lung transplantation. Characterization of transgene expression is not adversely affected by I/R injury or graft rejection. |
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AbstractList | Introduction: Gene therapy is effective in preventing ischemia-reperfusion injury and allograft rejection after experimental lung transplantation. Currently, no means exist to noninvasively determine the distribution, magnitude and timing of transgene expression after transplantation. This study utilizes a novel PET reporter gene system to characterize transgene expression after experimental lung transplantation.
Methods: Experiments utilized a rodent orthotopic left lung transplant model. Donors underwent endotracheal transfection 24 hours before harvest with 5x1010 VPs of adenovirus encoding a fusion gene of thymidine kinase (TK, PET reporter gene) and green fluorescent protein. PET images were obtained in 4 groups of recipients: 24 hours postoperatively with and without I/R injury, and 4 days postoperatively with and without acute rejection. Rats which underwent transfection alone served as controls. Excised lungs were assessed for gamma counter radioactivity and TK activity.
Results: Transplanted lungs displayed strong and linear correlation between PET signals and gamma counter radioactivity (r2 = 0.82, p < 0.01). PET imaging also correlated with tissue TK activity (r2 = 0.44, p < 0.01). There was no difference in apparent lung volumes by PET between transplanted lungs with and without I/R injury and rejection.
Conclusions: PET imaging is a sensitive and quantitative method for characterizing pulmonary transgene expression in experimental lung transplantation. Characterization of transgene expression is not adversely affected by I/R injury or graft rejection. |
Author | Dharmarajan, Sekhar Ishiyama, Takaaki Hayama, Makio Patterson, G.Alexander Schuster, Daniel |
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Title | In vivo molecular imaging characterizes pulmonary gene expression in experimental lung transplantation |
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