MIRDcell Version 3

美国食品和药物管理局批准α粒子发射放射性药物(RP)二氯化镉(Xofigo®)和 β粒子发射Lu177 DOTATE(Lutathera®)及其在临床上的成功实施， 有助于重新激发人们对癌症放射药物疗法(RPT)的兴趣。RPT需要 将放射性药物输送到原发肿瘤、转移瘤和播散性肿瘤细胞(DTC)。不同 放射性核素的种类一直被提倡用于治疗，包括α，β和俄歇发射体。不同的 这些辐射在组织中的范围以及它们在相对生物有效性(RBE)方面的差异 预测治疗效果的复杂性。-然而，就像外照射疗法一样，未来 RPT的好坏将在一定程度上取决于我们计划治疗的能力，以最大化治疗效果，同时将 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固有摄取不均匀会影响我们的灭菌能力 肿瘤、转移和DTC。虽然原发肿瘤通常可以通过外照射治疗 辐射、微转移和DTC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MIRDcell V2，已开发 在豪厄尔实验室与MIRD委员会合作，于2014年广泛使用。MIRDcell V2具有 优势和劣势。该项目试图通过创建MIRDcell V3来克服许多弱点 具有促进微转移瘤和DTC的RPT设计和治疗计划的新能力。此外, MIRDcell V3将作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 不同的放射性核素和其他参数预计会影响细胞杀伤。粒子的影响 可以探索范围、RBE、活度分布等参数。鉴于一项新的研究， 在其前身MIRDcell V2的推动下，这种教育元素可能是最重要的 MIRDcell V3的一些方面。

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.