MIRDcell Version 3

MIRDcell 版本 3

基本信息

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
项目类别：
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

项目摘要

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.

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。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)。已提倡使用不同类型的放射性核素进行治疗，包括α、β和俄歇发射体。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，就像外部放射治疗一样，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。 RPT 长期成功的关键是克服对正常组织的不利影响。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 通常可以通过外部光束来治疗。辐射、微转移和 DTC 不能，但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，仅开发了 MIRDcell V2。 2014 年，Howell 实验室与 MIRD 委员会合作，MIRDcell V2 已广泛使用。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。 MIRDcell V3 将成为剂量学和放射生物学不可或缺的教育工具学生将能够操作 MIRDcell V3 并了解如何选择放射性药物。不同的放射性核素和其他参数预计会影响细胞杀伤的影响。鉴于新的研究，可以探索范围、RBE、活性分布和其他参数。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。