Prevention of coronary restenosis using a radioactive stent: Radiobiological studies

Radiation therapy is currently under investigation as a therapeutic option for the prevention and the treatment of restenosis following percutaneous coronary interventions. Restenosis after vessel injury is associated with a transient state of cell proliferation and bears many similarities with wound healing. It is known that ionizing radiation can delay or impair wound healing. One proposed approach uses the deployment of a radioactive stent and continuous low dose-rate treatment. Our experimental studies have been conducted to better evaluate the radiobiology of vascular cells and as a preamble to the design of an original radioactive stent based on a 45Ca-DTPA polymer-coated stent.; We performed morphometric analysis of human coronary segments with restenosis. Most of vessel area was occupied by atherosclerotic plaque and neointima accounted for a limited part. Adventitial and medial thicknesses were significantly thinner than the atherosclerotic plaque and neointima. The medial layer was the most cellular. Our results indicated that target volumes for endovascular catheter-based brachytherapy or radioactive stents remain small. After delivery of doses such as proposed in the current experience, only a few thousand cells would remain clonogenic. Depending of the residual growth stimulus, this would create a permanent impairment or a significant delay in the healing and the restenosis process.; We compared in vitro responses of human and pig fibroblasts, smooth muscle cells and endothelial cells exposed to high dose-rate γ irradiation. Using clonogenic assays, growth inhibition and filter elution techniques, we found that human and pig cells have similar radiation responses. Our results suggest that vascular cell lines cover a broad range of radiosensitivities without specific differences between cell types.; We developed an experimental set-up to evaluate the in vitro effects of low energy β-emitters on vascular cells. The complex is the 45Ca-diethylenetriaminepentaacetate (45Ca-DTPA) with a maximal energy of 255 KeV. There was a good correlation between calculated doses and doses measured by dosimeters placed at the bottom of petri dishes. However, it seems that doses administered to cell monolayers would be better evaluated by the dose calculated by the Medical Internal Radiation Dose (MIRD) instead of half the calculated dose, as previously suggested.; We evaluated the dose-rate effect of vascular smooth muscle cells exposed to low dose-rate irradiation with the 45Ca-DTPA complex. (Abstract shortened by UMI.)...