Fabao Gao MD, Abstract Co-Author: Nothing to Disclose

Bensheng Qiu PhD, Abstract Co-Author: Nothing to Disclose

Sourav Kar, Abstract Co-Author: Nothing to Disclose

Xiangcan Zhan PhD, Abstract Co-Author: Nothing to Disclose

Lawrence Vincent Hofmann MD, Abstract Co-Author: Nothing to Disclose

Xiaoming Yang MD, PhD, Presenter: Nothing to Disclose

To validate a new technique using intravascular magnetic resonance (MR)/radiofrequency (RF) to enhance gene therapy of in-stent stenosis.

Via a catheter-based approach, we locally delivered vascular endothelial growth factor (VEGF-165) gene/lentivirus or green fluorescent protein (GFP) gene/lentivirus (as a control) into 22 (11-paired) femoral/iliac arteries of 11 pigs, which were fed a high cholesterol diet for two months. To compare VEGF and GFP genes, we transferred 1-mL VEGF/lentivirus into the unilateral femoral/iliac arteries and 1-mL GFP/lentivirus into the contralateral arteries. To compare MR/RF-heated VEGF and non-heated VEGF genes, we transferred 1-mL VEGF/lentivirus into each of the bilateral femoral/iliac arteries, while, during VEGF gene delivery, the left gene-targeted arteries were heated using an intravascular MR/RF system, and the right corresponding arteries were not heated to serve as controls. Immediately after the gene transfer, paired stents were placed in the bilateral, gene-targeted artery segments. At day 60 after gene/stent interventions, we harvested bilateral targeted arteries for pathology correlation.

The results showed the increased serum cholesterol from 103.3±35.5mg/dL at baseline to 602.1±319.5mg/dL at day 60 after gene/stent interventions. In the GFP versus VEGF group, x-ray angiographies showed in-stent stenoses in all GFP-treated arteries, while no obvious stenoses were visualized in VEGF-treated arteries. In the VEGF versus VEGF-RF group, angiography-detectable in-stent stenoses were found in three of five arteries treated with VEGF genes only, while no in-stent stenoses were detected in any arteries treated by VEGF genes plus MR/RF heating. Correlative microscopy showed that the average thickness of in-stent neointimal hyperplasia was 306% thinner in VEGF-treated arteries than in GFP-treated arteries (P < 0.01), and 138% thinner in VEGF/RF-treated arteries than in VEGF-treated arteries (P < 0.01).

Intravascular MR/RF-heating offers great potential to enhance gene therapy of in-stent restenosis.

Gao, F, Qiu, B, Kar, S, Zhan, X, Hofmann, L, Yang, X, Intravascular Magnetic Resonance/Radiofrequency-enhanced Gene Therapy of Atherosclerotic In-stent Stenosis.  Radiological Society of North America 2004 Scientific Assembly and Annual Meeting, November 28 - December 3, 2004 ,Chicago IL. http://archive.rsna.org/2004/4402981.html