TOOL TO ADJUST FOR SOURCE DECAY IN VACULAR IRRADIATION

在美国，每年有近40万名患者接受球囊血管成形术 以改善动脉血流。其中约40%的手术 不成功是因为再狭窄，这估计会使 美国的医疗保健系统每年大约有8-20亿美元。 血管内照射是一种新的创新方法，提供了 有效预防再狭窄的潜力。 几乎所有已使用/建议的放射性核素都具有较短的放射性半衰期- 因此，在信号源的使用寿命内，曝光时间必须 由于震源活跃度的下降而不断扩大。 因为接触的时间相当于亚致死的一半时间 损伤修复(T1/2)，特定剂量的生物效应会有所不同 在信号源的实际生命周期内显著增加。 我们的目标是生产一个可靠的、用户友好的软件工具，允许 医生要找到最佳的方法来调整给定的减少 在源的活度(因此也就是剂量率)中， 生物效应将保持不变。所需的基本信息 目标单元格的T1/2与其他相关 放射生物学反应参数(α/β)。在第一阶段，这些将 对一株人冠状动脉平滑肌细胞系的测定 并将编写和评估一个试点计算机程序，以 调整暴露时间以获得恒定的生物有效剂量 随着放射源的衰变和治疗时间的不同。 建议的商业应用 再狭窄给美国医疗系统造成的损失约为8-20亿美元 美元/年。血管照射是一种潜在的新技术 提供有效的再狭窄预防，并可能有 应用广泛。因为放射源使用了衰变 它们的使用寿命，一种灵活的工具，使基于生物的 调整剂量处方以适应剂量率的变化 必不可少的。

In the US, almost 400,000 patients annually receive balloon angioplasty to improve arterial blood flow. About 40 percent of these procedures are unsuccessful because of restenosis, which is estimated to cost the US health care system approximately 0.8-2 billion dollars annually. Endo-vascular irradiation is a new and innovative approach offering the potential of effective restenosis prevention. Almost all the used/proposed radionuclides have short radioactive half- lives so that, during the useful life of the source, exposure times must be continuously extended because of the decreasing source activity. Since the exposure times are comparable to the half-time of sublethal damage repair (T1/2), the biological effect of a given dose will vary significantly over the practical lifetime of the source. The goal is to produce a reliable user-friendly software tool allowing the physician to find the optimal way to adjust for a given reduction in the activity (and therefore the dose rate) of the source, so that the biological effect will remain unchanged. The basic information required is the T1/2 of the target cells, together with the other relevant radiobiological response parameter (alpha/beta). In Phase I, these will be determined for one coronary artery smooth muscle cell line of human origin, and a pilot computer program will be written and assessed, to adjust exposure times to obtain a constant biologically effective dose as the radioactive source decays and treatment times vary. PROPOSED COMMERCIAL APPLICATION Restenosis costs the US health care system approximately 0.8-2 billion dollars/yr. Vascular irradiation is a new technique potentially offering effective restenosis prevention, and is likely to have widespread application. Because the radioactive sources used decay over their useful lifetime, a flexible tool giving biologically-based adjustments in the dose prescription for changes in dose rate will be essential.