Magnetic Resonance Imaging Permits In Vivo Monitoring of Catheter-Based Vascular Gene Delivery

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Abstract
Background Gene therapy is an exciting frontier in modern medicine. To date, most investigations about the imaging of gene therapy have primarily focused on noncardiovascular systems, and no in vivo imaging modalities are currently available for monitoring vascular gene therapy. The purpose of this study was to develop an in vivo imaging tool to monitor a catheter-based vascular gene delivery procedure. Methods and Results We produced gadolinium/blue dye and gadolinium/gene-vector media by mixing Magnevist with a trypan-blue or a lentiviral vector carrying a green fluorescent protein (GFP) gene. The gadolinium was used as an imaging marker for magnetic resonance (MR) imaging to visualize vessel wall enhancement, and the blue dye/GFP was used as a tissue stain marker for histology/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 were monitored under high-resolution MR imaging. The results showed, in all 12 pigs, the gadolinium enhancement of the target vessel walls on MR imaging and the blue/GFP staining of the target vessel tissues with histology/immunohistochemistry. This study shows the potential of using MR imaging to dynamically visualize (1) where the gadolinium/genes are delivered; (2) how the target portion is marked; and (3) whether the gene transfer procedure causes 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.