MIRDcell Version 3

MIRDcell 版本 3

• 批准号: 10320949
• 负责人: Roger W. Howell
• 金额: $ 11.76万
• 依托单位: RBHS-NEW JERSEY MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-15 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10320949
• 关键词: 3-Dimensional; Address; Adverse effects; Advocate; Affect; Algorithms; Alpha Particle Emitter; Basic Science; Beta Particle; Biological; Bystander Effect; Cell Compartmentation; Cell Nucleus; Cell membrane; Cells; Classification; Clinic; Code; Collaborations; Collection; Custom; Cytoplasm; Data; Development Plans; Dimensions; Disease; Distributional Activity; Dose; Dose-Rate; Education; Elements; External Beam Radiation Therapy; Fibroblasts; Future; High-LET Radiation; Image; Label; Learning; Lutetium; Malignant Neoplasms; Micrometastasis; Microscopic; Modeling; Neoplasm Metastasis; Normal tissue morphology; Output; Photons; Primary Neoplasm; Probability; Radiation; Radiation Tolerance; Radioactivity; Radiobiology; Radioisotopes; Radiopharmaceuticals; Radium; Relative Biological Effectiveness; Research; Rotation; Schedule; Slice; Software Tools; Speed; Students; Surface; Testing; Therapeutic Effect; Tissues; To specify; Tomogram; Treatment Efficacy; United States Food and Drug Administration; Update; Visual; Work; base; cancer cell; cancer therapy; cell killing; cell type; design; dosimetry; flexibility; improved; individualized medicine; innovation; intercellular communication; interest; neoplastic cell; novel; particle; predicting response; response; success; therapy design; tool; treatment planning; tumor; uptake; usability

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.

USFDA批准α粒子放射性药物（RP）镭223二氯化物（Xofigo®）和 发射β粒子的镥177 dotatate（LUTATHERA®）及其在临床上的成功应用， 有助于重振对癌症的放射性药物治疗（RPT）的兴趣。RPT需要 将放射性药物递送至原发性肿瘤、转移瘤和播散性肿瘤细胞（DTC）。不同 已经提倡使用包括α、β和俄歇发射体的放射性核素的种类进行治疗。不同 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，像外部光束放射治疗，未来 的RPT将部分取决于我们计划治疗的能力，最大限度地提高治疗效果， 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固有不均匀吸收，这可能影响我们的杀菌能力 肿瘤、转移和DTC。虽然原发性肿瘤通常可以用外部光束治疗， 放射、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，并使用它来预测反应， 缺乏可用于优化和规划微观疾病RPT的工具。只有MIRDcell V2，开发 在豪厄尔实验室与MIRD委员会在2014年合作，广泛使用。MIRDcell V2具有 优点和缺点。该项目旨在通过创建MIRDcell V3来克服许多弱点 具有新的功能，以促进微转移和DTC的RPT设计和治疗计划。此外，本发明还提供了一种方法， MIRDcell V3将作为辐射剂量学和放射生物学的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 预期不同的放射性核素和其它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。鉴于新的研究， 受其前身MIRDcell V2的启发，这种教育元素可能是最重要的元素之一 MIRDcell V3的特性。