[Intravascular irradiation in the combined therapy and prevention of restenosis. Overview]

Despite numerous efforts in catheter technology and procedural approaches the problem of restenosis in interventional cardiology persists. Although the implantation of coronary stents has significantly reduced restenosis rates based on the inhibition of elastic recoil, intimal proliferation as the second major mechanism for postinterventional restenosis could not effectively be suppressed. Intimal proliferation is the response to vessel injury following interventional procedure, e.g. balloon angioplasty. It results in the adhesion of mono- and lymphocytes which themselves trigger the colonisation of myofibroblasts. Intracoronary irradiation seeks to prevent this proliferative process as it destroys or irreversibly alters DNA structures of cells at the site of balloon injury. The antiproliferative effect depends on the irradiation dosis, the timing and the cell cycle phase. Mainly beta- and gamma-radiation is used for intracoronary irradiation. Beta-emitters are characterized by a sharp decline of dose rate within millimeters from the actual source. The exposure to surrounding tissue as well the catheter staff can be kept to a minimum. The high intensity of beta-emitters allow a short treatment period of minutes to gain an effective radiation dose to the target. In contrast, gamma-emitters have a low radial dose distribution resulting in high dosage even centimeters away from the source. These emitters require additional shielding in the catheter laboratory and lead to excessive whole body doses. To achieve a sufficient dose in the target tissue, irradiation times of more than 20 minutes are necessary which prolongs the interventional procedure substantially. At present, catheter based systems or radioactive implantable stents are available to deliver the required dose. Catheter based systems seem more flexible in a number of considerations. On the other hand they require a substantial amount of hardware. Beta-emitting stents are implanted via a conventional stent delivery system with small shielding modifications. However, stents emit an inhomogeneous radiation profile due to the mesh-like structure. In addition, not every lesion can be reached by a stent nor does every lesion require a stent solely to deliver radiation. External irradiation is presently not recommended due to its ineffectiveness and the high rate of side effects. In the experimental setting the porcine model comes closest to the clinical situation in man. Animal experiments have demonstrated the effective reduction of intimal proliferation using beta- and gamma-sources in a wide dose range of 3 to 56 Gy. Although the initial and early results are convincing little is know about the long term results. Only few studies have been and are currently performed in patients. Some of these investigations demonstrate a significant reduction of restenosis rate after 6 months. Again, information on long-term results are lacking. It has to be considered that perivascular fibrosis, which may occur with a delay of 5 to 10 years depending on the dosage, could curtail the initial success. Intracoronary irradiation is a promising method for the prevention of restenosis. The dose finding with respect to the dose effect relation, the determination of the therapeutic window and the timing of irradiation have to be further defined in the clinical setting. Nevertheless, intracoronary irradiation remains high on the priority list in fighting restenosis.