Radionuclides conjugated to molecules that bind specifically to cancer cells are of great interest as a means to increase the specificity of radiotherapy. Currently, the methods to disseminate these targeted radiotherapeutics have been either systemic delivery or by bolus injection into the tumor or tumor resection cavity. Herein we model a potentially more efficient method of delivery, namely pressure-driven fluid flow, called convection-enhanced delivery (CED), where a device infuses the molecules in solution (or suspension) directly into the tissue of interest. In particular, we focus on the setting of primary brain cancer after debulking surgery, where the tissue margins surrounding the surgical resection cavity are infiltrated with tumor cells and the most frequent sites of tumor recurrence. We develop the combination of fluid flow, chemical kinetics, and radiation dose models needed to examine such protocols. We focus on Auger electron-emitting radionuclides (e.g. 67Ga, 77Br, 111In, 125I, 123I, 193mPt, 195mPt) whose short range makes them ideal for targeted therapy in this setting of small foci of tumor spread within normal tissue. By solving these model equations, we confirm that a CED protocol is promising in allowing sufficient absorbed dose to destroy cancer cells with minimal absorbed dose to normal cells at clinically feasible activity levels. We also show that Auger emitters are ideal for this purpose while the longer range alpha particle emitters fail to meet criteria for effective therapy (as neither would energetic beta particle emitters). The model is used with simplified assumptions on the geometry and homogeneity of brain tissue to allow semi-analytic solutions to be displayed, and with the purpose of a first examination of this new delivery protocol proposed for radionuclide therapy. However, we emphasize that it is immediately extensible to personalized therapy treatment planning as we have previously shown for conventional CED, at the price of requiring a fully numerical computerized approach.

中文翻译：

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用于优化将靶向放射性核素疗法递送到切除腔边缘以治疗原发性脑癌的模型

与与癌细胞特异性结合的分子结合的放射性核素作为提高放射治疗特异性的手段引起了人们极大的兴趣。目前，传播这些靶向放射治疗剂的方法是全身给药或通过推注注射到肿瘤或肿瘤切除腔中。在此，我们模拟了一种可能更有效的输送方法，即压力驱动的流体流动，称为对流增强输送 (CED)，其中设备将溶液（或悬浮液）中的分子直接注入感兴趣的组织。我们特别关注减瘤手术后原发性脑癌的情况，其中手术切除腔周围的组织边缘被肿瘤细胞浸润，是肿瘤复发最常见的部位。我们开发了流体流动的组合，检查此类协议所需的化学动力学和辐射剂量模型。我们专注于俄歇电子发射放射性核素（例如 67Ga、77Br、111In、125I、123I、193mPt、195mPt），其射程短，非常适合在正常组织内肿瘤扩散的小病灶环境中进行靶向治疗。通过求解这些模型方程，我们确认 CED 协议有希望允许足够的吸收剂量以在临床上可行的活性水平对正常细胞的最小吸收剂量来破坏癌细胞。我们还表明，俄歇发射器是实现此目的的理想选择，而较长距离的 α 粒子发射器无法满足有效治疗的标准（因为高能 β 粒子发射器也不符合）。该模型与脑组织几何形状和同质性的简化假设一起使用，以允许显示半分析解，目的是首次检查为放射性核素治疗提出的这种新的传输协议。然而，我们强调它可以立即扩展到个性化治疗计划，正如我们之前为传统 CED 展示的那样，代价是需要完全数字化的计算机化方法。