Magnetic resonance imaging permits in vivo monitoring of catheter-based vascular gene delivery

Background-Gene therapy is an exciting frontier in modern medicine. To date , most investigations about the imaging of gene therapy have primarily focu sed on noncardiovascular systems, and no in vivo imaging modalities are cur rently available for monitoring vascular gene therapy. The purpose of this study was to develop an in vivo imaging tool to monitor a catheter-based va scular gene delivery procedure. Methods and Results-We produced gadolinium/blue dye and gadolinium/gene-vec tor media by mixing Magnevist with a trypan-blue or a lentiviral vector car rying a green fluorescent protein (GFP) gene. The gadolinium was used as an imaging marker for magnetic resonance (MR) imaging to visualize vessel wal l enhancement, and the blue dye/GFP was used as a tissue stain marker for h istology/immunohistochemistry to confirm the success of the transfer. Using Remedy gene delivery catheters, we transferred the gadolinium/blue dye (n= 8) or gadolinium/GFP lentivirus (n=4) into the arteries of 12 pigs, that we re monitored under high-resolution MR imaging. The results showed, in all 1 2 pigs, the gadolinium enhancement of the target vessel walls on MR imaging and the blue/GFP staining of the target vessel tissues with histology/immu nohistochemistry. This study shows the potential of using MR imaging to dyn amically visualize (1) where the gadolinium/genes are delivered; (2) how th e target portion is marked; and (3) whether the gene transfer procedure cau ses complications. Conclusions-We present a technical development that uses high-resolution MR imaging as an in vivo imaging tool to monitor catheter-based vascular gene delivery.