ABSTRACT
Hemodialysis vascular access dysfunction as a result of venous neointimal hyperplasia in dialysis access grafts and fistulae is currently a huge clinical problem. The aim of this study was to assess the effects of paclitaxel and radiation, both singly and in combination on the proliferation of cell types present within the lesion of venous neointimal hyperplasia (vascular smooth muscle cells, fibroblasts and endothelial cells within the neointimal microvessels). Vascular smooth muscle cells, fibroblasts and endothelial cells were plated onto 96-well plates and exposed to different concentrations and doses of paclitaxel and radiation, respectively (both individually and in combination). Growth inhibition was assessed with an MTT assay. Both paclitaxel and radiation resulted in significant growth inhibition of all three cell types. However, even small doses of paclitaxel appeared to attenuate the antiproliferative effect of radiation on these cell types. Further experiments to elucidate the mechanism behind these findings could result in a better understanding of combination antiproliferative therapies.
Subject(s)
Arteriovenous Shunt, Surgical/adverse effects , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Graft Occlusion, Vascular/prevention & control , Muscle, Smooth, Vascular/cytology , Paclitaxel/pharmacology , Cells, Cultured , Endothelial Cells/drug effects , Endothelial Cells/radiation effects , Fibroblasts/drug effects , Fibroblasts/radiation effects , Humans , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/radiation effectsABSTRACT
PURPOSE: Optimization of intravascular radiation to reduce stenosis following coronary angioplasty requires the ability to predict the patterns of radiation dose distribution. This investigation evaluated the agreement between Monte Carlo simulations and experimental radiation dose measurements for a radioisotope liquid-filled balloon catheter in a tissue equivalent phantom. METHODS AND MATERIALS: Direct measurements of the radiation dose from Re-186 liquid-filled balloons were made using thermoluminescent dosimeters (TLDs) and radiochromic film. Monte Carlo simulations were carried out using the Monte Carlo N-Particle code system (MCNP4B). RESULTS: The Monte Carlo generated dose values agreed with the experimentally determined results within the statistical uncertainty. A slightly higher penetration was indicated by regression analysis for the TLD data relative to the MCNP4B prediction that may be due to experimental configuration anomalies. For this balloon catheter, approximately 55 mCi of Re-186 will deliver 15 Gy at a 0.5 mm depth in tissue equivalent material in 5 min. CONCLUSIONS: Correlation between experimentally measured dose values and Monte Carlo computation supports the position that MCNP4B simulations constitute a valuable tool for investigating various clinical therapy designs. The agreement between Monte Carlo calculations and experiments provide confidence in applying MCNP4B to more sophisticated geometries of interest, and other methods of intravascular radiation dose delivery.
