In vivo molecular imaging characterizes pulmonary gene expression in experimental lung transplantation

Abstract

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 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.