Department of Radiation Oncology, Dana Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Int J Radiat Oncol Biol Phys. 2010 Feb 1;76(2):615-23. doi: 10.1016/j.ijrobp.2009.06.039. Epub 2009 Oct 30.
Implantable devices routinely used for increasing spatial accuracy in modern image-guided radiation treatments (IGRT), such as fiducials or brachytherapy spacers, encompass the potential for in situ release of biologically active drugs, providing an opportunity to enhance the therapeutic ratio. We model this new approach for two types of treatment.
Radiopaque fiducials used in IGRT, or prostate brachytherapy spacers ("eluters"), were assumed to be loaded with radiosensitizer for in situ drug slow release. An analytic function describing the concentration of radiosensitizer versus distance from eluters, depending on diffusion-elimination properties of the drug in tissue, was developed. Tumor coverage by the drug was modeled for tumors typical of lung stereotactic body radiation therapy treatments for various eluter dimensions and drug properties. Six prostate (125)I brachytherapy cases were analyzed by assuming implantation of drug-loaded spacers. Radiosensitizer-induced subvolume boost was simulated from which biologically effective doses for typical radiosensitizers were calculated in one example.
Drug distributions from three-dimensional arrangements of drug eluters versus eluter size and drug properties were tabulated. Four radiosensitizer-loaded fiducials provide adequate radiosensitization for approximately 4-cm-diameter lung tumors, thus potentially boosting biologically equivalent doses in centrally located stereotactic body treated lesions. Similarly, multiple drug-loaded spacers provide prostate brachytherapy with flexible shaping of "biologically equivalent doses" to fit requirements difficult to meet by using radiation alone, e.g., boosting a high-risk region juxtaposed to the urethra while respecting normal tissue tolerance of both the urethra and the rectum.
Drug loading of implantable devices routinely used in IGRT provides new opportunities for therapy modulation via biological in situ dose painting.
在现代图像引导放射治疗（IGRT）中，常规使用植入式设备来提高空间精度，例如基准标记或近距离放射治疗间隔物，这些设备有可能在原位释放具有生物活性的药物，从而有机会提高治疗比率。我们为两种治疗方法建立了这种新方法的模型。
IGRT 中使用的放射不透性基准标记或前列腺近距离放射治疗间隔物（“洗脱器”）被假定为加载了放射增敏剂，以实现药物的原位缓慢释放。开发了一种解析函数，用于描述距离洗脱器的距离与放射增敏剂浓度之间的关系，该函数取决于药物在组织中的扩散-消除特性。针对各种洗脱器尺寸和药物特性，针对典型的肺部立体定向体部放射治疗肿瘤，对药物的肿瘤覆盖范围进行了建模。通过假设植入载药间隔物，对 6 例前列腺（125）I 近距离放射治疗病例进行了分析。模拟了放射增敏剂诱导的亚体积增强，从中计算了典型放射增敏剂的生物有效剂量，在一个示例中进行了计算。
列出了药物洗脱器的三维排列方式与洗脱器尺寸和药物特性的药物分布情况。四个载药基准标记可以为直径约 4 厘米的肺部肿瘤提供足够的放射增敏作用，从而有可能在位于中心的立体定向体治疗病变中增强生物等效剂量。类似地，多个载药间隔物可使前列腺近距离放射治疗灵活地形成“生物等效剂量”，以满足仅用辐射难以满足的要求，例如，在毗邻尿道的高风险区域进行增强，同时尊重尿道和直肠的正常组织耐受性。
常规用于 IGRT 的植入式设备的药物加载为通过生物原位剂量描绘提供了新的治疗调制机会。
