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OBJECTIVE Radiation therapy is undergoing extensive preclinical and clinical testing as a new tool to reduce restenosis after vessel injury. To date, however, no definite dose threshold has been identified after radioactive stent implantation. In this study, we compared the in vitro response of pig vascular smooth muscle cells (SMC) to conventional high-dose-rate (HDR) irradiation with the response to continuous low-dose rate (LDR) that could result from exposure to a radioactive stent. METHODS Catheter-based radiotherapy delivers single doses at HDR whereas radioactive stents use a continuous LDR approach. Single doses in excess of 10 Gy have clearly shown a reduction in neointima formation and negative vessel remodeling in several animal models. Because dose rate is an important parameter modulating the overall biological response to ionizing radiation, we have compared the in vitro response of pig aortic SMC at conventional HDR (1.5 Gy/min) and at LDR (0.675 Gy/h). RESULTS SMC showed significant repair of sublethal DNA damage and about twice the dose was necessary at the LDR to produce the same effect as that seen at the HDR. CONCLUSIONS In vitro SMC exhibit a significant dose-rate effect that indicates that radioactive stents could deliver the dose at a sufficiently high dose rate to compensate for cell proliferation while at the same time the total dose should be increased to account for sublethal damage repair. This finding has important implications for the design of a radioactive stent.
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