RADIATION ENHANCEMENT WITH IODINATED DEOXYURIDINE

常规光子放射治疗的一种辐射增强技术 概述。 高线性能量转移（LET）辐射， 俄歇电子分布是由光子束通过 作为胸苷类似物掺入的稳定碘的光活化 (Tyd)在DNA中。 在评价的几种卤代脱氧核糖核苷中， 选择碘化脱氧尿苷（IdUrd）作为唯一的Tyd类似物， 有效的原位光活化。 该机制与 由IdUrd产生的辐射致敏作用，以产生总体辐射 增强 计算表明，肿瘤DNA中5%的Tyd替换应该成倍增加， 低能量光子的生物有效性提高了2倍。 更高的更替率将带来更高的收益。 增强结果来自 IdUrd的化学致敏作用，其中已知 辐射乘以1.5 - 3的因子作为替换 从5%到50%不等。 额外的增强效果来自于刺激 DNA中的俄歇级联。 年， 体内人肿瘤。 在小鼠肿瘤中至少获得了15%。 我们 已经能够记录各种放射生物学参数， 我们的分析（敏化，光活化）使用单细胞培养。 特别是，我们的数据显示，致敏（以及 光活化）不能修复。 因此，预计使用低 与Sm-145源的"永久性"注入有关的剂量率（38 - 45 KeV X射线; T 1/2 = 34 d）将产生额外的治疗增加 有效性为3 - 8倍，与急性 剂量率。 预期之前的良好临床结果 与BrdUrd和高能X射线可以进一步改善通过使用 的IdUrd和合适的较低能量激活光子（35 - 50 keV）。 用注入源（如从Sm-145获得的源）进行的持续辐照 可以在所选部位如大脑或头部提供独特的优势， 颈部肿瘤 这里描述的实验旨在完成我们对 相关参数，并在两只动物中测试治疗方式 肿瘤模型

A technique for radiation enhancement of conventional photon radiotherapy is outlined. High Linear Energy Transfer (LET) radiations in the form of Auger electron distributions are generated by a photon beam through photoactivation of stable iodine incorporated as an analog of thymidine (Tyd) in DNA. Of the several halogenated deoxyribonucleosides evaluated, iodinated deoxyuridine (IdUrd) is chosen as the only Tyd analog providing effective photoactivation in situ. This mechanism is combined with radiation sensitization produced by IdUrd to produce an overall radiation enhancement. Calculations show that 5% replacement of Tyd in tumor DNA should multiply the biological effectiveness of low energy photons by a factor of 2. Higher replacements would provide higher gains. Enhancement results from chemical sensitization by IdUrd, where it is known that effects of irradiation are multiplied by factors of from 1.5 to 3 as replacement varies from 5 to 50%. Additional enhancement results from the stimulation of Auger cascades in DNA. Five percent replacement has been obtained in human tumor in vivo. At least 15% has been obtained in murine tumors. We have been able to document the various radiobiological parameters used in our analysis (sensitization, photoactivation) using single cell cultures. In particular, our data show that damage from sensitization (as well as photoactivation) does not repair. Thus it is anticipated that use of low dose rates associated with "permanent" implants of Sm-145 sources (38-45 KeV x-rays; T 1/2 = 34 d) will yield an additional increase in therapeutic efficacy by a factor of from 3 to 8, compared to that obtained with acute dose rates. The expectation is that previous favorable clinical results with BrdUrd and high energy x-rays can be further improved through the use of IdUrd and suitable lower energy activating photons (35 - 50 keV). Protracted irradiations with implanted sources such as obtained from Sm-145 may provide unique advantages at selected sites such as brain, or head and neck tumors. The experiments described here are designed to complete our compilation of relevant parameters, and to test the therapeutic modality in two animal tumor models.