MIRDcell Version 3

美国 FDA 批准发射 α 粒子的放射性药物 (RP) 二氯化镭 223 (Xofigo®) 和 发射 β 粒子的镥 177 dotatate (LUTATHERA®) 及其在临床中的成功实施， 重新激发了人们对癌症放射性药物治疗（RPT）的兴趣。 RPT 需要 将放射性药物递送至原发肿瘤、转移瘤和播散性肿瘤细胞 (DTC)。不同 已提倡使用多种类型的放射性核素进行治疗，包括 α 、β 和俄歇发射体。不同的 这些辐射在组织中的范围及其相对生物有效性（RBE）的差异，有助于 预测治疗效果的复杂性。 ‐然而，就像外照射放射治疗一样，未来 RPT 的效果部分取决于我们规划治疗的能力，以最大限度地提高治疗效果，同时最大限度地减少治疗效果。 对正常组织的不良影响。 RPT 长期成功的关键是克服 癌细胞对放射性药物的内在不均匀吸收可能会影响我们的灭菌能力 肿瘤、转移瘤和 DTC。虽然原发性肿瘤通常可以通过外部光束来治疗 放射、微转移和 DTC 则不能。虽然有商业工具可以帮助计算 基于外部成像的宏观疾病的吸收剂量并用它来预测反应，有一个 缺乏可用于优化和规划微观疾病 RPT 的工具。仅开发 MIRDcell V2 2014 年，Howell 实验室与 MIRD 委员会合作，该技术已得到广泛应用。 MIRDcell V2 有 优点和缺点。该项目旨在通过创建 MIRDcell V3 来克服许多弱点 具有促进微转移和 DTC 的 RPT 设计和治疗计划的新功能。此外， MIRDcell V3 将成为剂量学和放射生物学不可或缺的教育工具 放射性药物。学生将能够操作 MIRDcell V3 并了解如何选择 预计不同的放射性核素和其他参数会影响细胞杀伤。粒子的影响 范围、RBE、活性分布和其他参数都可以探索。鉴于新的研究表明 受到其前身 MIRDcell V2 的推动，这种教育元素也许是最重要的元素之一 MIRDcell V3 的各个方面。

The USFDA approval of the α particle emitting radiopharmaceutical (RP) radium 223 dichloride (Xofigo®) and the β-particle emitting lutetium 177 dotatate (LUTATHERA®), and their successful implementation in the clinic, has contributed to reinvigorated interest in radiopharmaceutical therapy (RPT) of cancer. RPT entails the delivery of radioactive drugs to the primary tumor, metastases, and disseminated tumor cells (DTC). Different classes of radionuclides have been advocated for therapy including α , β , and Auger emitters. The different ranges of these radiations in tissue, and their differences in relative biological effectiveness (RBE), contribute to the complexity of predicting therapeutic efficacy. ‐However, like external beam radiation therapy, the future of RPT will depend in part on our capacity to plan treatments that maximize therapeutic effect while minimizing adverse effects in normal tissues. Key to the long term success of RPT is to overcome limitations of the intrinsic nonuniform uptake of the radiopharmaceutical by cancer cells that can impact our capacity to sterilize tumors, metastases, and DTC. While primary tumors can often be addressed with external beams of radiation, micrometastases and DTC cannot. While there are commercial tools to assist with calculating absorbed dose to macroscopic disease based on external imaging and using it to predict response, there is a dearth of tools that can be used to optimize and plan RPT of microscopic disease. Only MIRDcell V2, developed in the Howell lab in collaboration with the MIRD Committee in 2014, is widely available. MIRDcell V2 has strengths and weaknesses. This project seeks to overcome many of the weaknesses by creating MIRDcell V3 with new capabilities to facilitate RPT design and treatment planning of micrometastases and DTC. In addition, MIRDcell V3 will serve as an indispensable educational tool for dosimetry and radiobiology of radiopharmaceuticals. Students will be able to operate MIRDcell V3 and learn about how the selection of different radionuclides and other parameters are expected to affect cell killing. The influence of particle range, RBE, activity distribution and other parameters can be explored. In view of the new research that was spurred by its predecessor, MIRDcell V2, this educational element is perhaps one of the most important aspects of MIRDcell V3.