Quantitative SPECT of Difficult to Image Therapeutic Radionuclides: An Extensible Cloud-Based Framework

难以成像的治疗性放射性核素的定量 SPECT：可扩展的基于云的框架

• 批准号: 9622938
• 负责人: ERIC C. FREY
• 金额: $ 30万
• 依托单位: RADIOPHARMACEUTICAL IMAGING AND DOSIMETRY, LLC
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9622938
• 关键词: 90Y; Algorithms; American; Biodistribution; CD22 gene; Calibration; Cell Nucleus; Chelating Agents; Clinical; Clinical Data; Clinical Trials; Clinical Trials Design; Code; Collimator; Complex; Computer software; Data; Daughter; Development; Diagnostic; Diagnostic Imaging; Distributional Activity; Dose; ERBB2 gene; Environment; European; FGFR2 gene; FOLH1 gene; Financial compensation; Foundations; Gamma Cameras; Goals; Growth; Health Services Accessibility; Healthcare; Image; Image Analysis; Indium-111; Investments; Laboratories; Libraries; Metastatic Neoplasm to the Bone; Metastatic Prostate Cancer; Methods; Modality; Modeling; Monitor; New Agents; Normal tissue morphology; Online Systems; Organ; Parents; Patients; Penetration; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase I Clinical Trials; Photons; Positron-Emission Tomography; Process; Radiation; Radioisotopes; Radionuclide Imaging; Radionuclide therapy; Radiopharmaceuticals; Regulation; Reporting; Research; Research Personnel; Resistance; Running; Scheme; Services; Software Framework; Speed; System; Technetium 99m; Technology; Therapeutic; Time; Tumor Tissue; Universities; Variant; Vendor; Work; base; cancer cell; cancer therapy; cloud based; design; dosimetry; experimental study; image reconstruction; improved; interest; optical spectra; precision medicine; programs; quantitative imaging; receptor; reconstruction; response; simulation; single photon emission computed tomography; software systems; success; targeted agent; tool; tumor; web interface

Radiopharmaceutical therapy (RPT) is an emerging cancer treatment that delivers radiation directly to cancer cells. The recent commercial success of 223Ra(Xofigotm) for resistant metastatic prostate cancer provides an example of the therapeutic and commercial potential of this modality. In addition, drug companies have large libraries of targets and targeting molecules. Progress in chelators and commercial availability of alpha emitters such as 212Pb and 227Th all are indicators that RPT is poised to become an important tool for cancer therapy. Several companies and academic centers are developing drugs based on alpha emitters. For example, Bayer has presented data on Th-227 based agents targeting CD22, HER2, PSMA and FGFR2 receptors. The 2017 BCC Research report “Radiopharmaceutical: Technologies and Global Markets”, says that the global radiopharmaceuticals market will grow at a 12.4% Compound Annual Growth Rate (CAGR) to $11.6B in 2021. The North American market will increase to $6.1B in 2021, a CAGR of 11.9%. During the past decade interest in therapeutic radiopharmaceuticals has increased. The diagnostic applications sector is expected to grow at 10% per year. Growth of Therapeutic RPTs of 22% per year is expected, driven by new radionuclides and approval of new αRPTs (e.g., Xofigo, Bayer HealthCare). Currently, there are 64 RPT drugs in various stages of development. Clinicaltrials.gov lists more than 100 trials investigating this modality; more than 20 pharmaceutical companies are working on RPTs, including large companies such as Roche/Genetech, and Bayer/Algeta. FDA approval of RPT agents requires tumor and normal tissue dose estimates. European regulations mandate personalized dosimetry. Optimal use of RPTs requires a precision medicine approach based on quantitative imaging and dosimetry. The foundation of this personalized dosimetry approach is quantitative imaging. Commercial quantitative SPECT/CT software packages have recently become available, but are designed for diagnostic radiopharmaceuticals, and the methods used are too simple to allow accurate quantitative reconstructions of therapeutic radionuclides. Methods to reconstruct these difficult-to-image radionuclides are not commercially available, and packages developed in academic laboratories are difficult to use and extend. The overall goal of this project is to demonstrate feasibility of developing and validating a commercial-grade, web-based, extensible quantitative reconstruction software framework for therapeutic radionuclides. To this end, we propose to (1) investigate algorithmic improvements to improve accuracy for high-energy emissions; (2) speed up the codes using multi-core CPUs and GPUs; (3) implement a web-based user interface that enables running reconstructions in a cloud-based environment and (4) validate the methods for 227Th and 212Pb using physical experiments on cameras from multiple vendors and realistic simulations. Successful completion of this would enable development of a Phase II quantitative reconstruction service essential in development and approval of RPTs and ultimately in delivery of optimal personalized dosing in a precision medicine paradigm.

放射性药物治疗（RPT）是一种新兴的癌症治疗方法，直接向癌症提供放射治疗 细胞最近223 Ra（Xofigotm）在治疗耐药转移性前列腺癌方面取得的商业成功提供了一个 这是该模式的治疗和商业潜力的示例。此外，制药公司拥有大量 靶和靶向分子的文库。螯合剂的研究进展和α发射体的商业化利用 例如212 Pb和227 Th都表明RPT有望成为癌症治疗的重要工具。 一些公司和学术中心正在开发基于α发射体的药物。例如，拜耳 发表了靶向CD 22、HER 2、PSMA和FGFR 2受体的Th-227类药物的数据。2017年 BCC研究报告《放射性药物：技术和全球市场》指出， 放射性药物市场将以12.4%的复合年增长率（CAGR）增长，到2021年达到116亿美元。 北美市场将在2021年增加到61亿美元，复合年增长率为11.9%。在过去的十年里， 放射性治疗药物的使用率有所上升。诊断应用部门预计将增长 每年10%。由于新的放射性核素的推动，治疗性RPT预计每年增长22%， 批准新的α RPT（例如，Xofigo，Bayer HealthCare）。目前，有64种RPT药物处于不同阶段， 发展Clinicaltrials.gov列出了100多个研究这种方法的试验; 20多个药物试验。 一些公司正在研究RPT，包括Roche/Genetech和Bayer/Algeta等大公司。FDA RPT药剂的批准需要肿瘤和正常组织剂量估计。欧洲法规要求 个性化剂量测定。RPT的最佳使用需要基于定量的精确医学方法， 成像和剂量测定。这种个性化剂量测定方法的基础是定量成像。 商业定量SPECT/CT软件包最近已经变得可用，但是被设计用于 诊断放射性药物，使用的方法过于简单，无法进行准确的定量 治疗性放射性核素的重建。重建这些难以成像的放射性核素的方法有 在商业上不可用，并且在学术实验室中开发的软件包难以使用和扩展。 该项目的总体目标是证明开发和验证商业级， 用于治疗性放射性核素的基于网络的可扩展定量重建软件框架。为此目的， 我们建议：（1）研究算法改进，以提高高能量发射的准确性;（2） 使用多核CPU和GPU加速代码;（3）实现基于Web的用户界面， 在基于云的环境中运行重建，以及（4）使用以下方法验证227 Th和212 Pb的方法 对多家供应商的相机进行物理实验和逼真的模拟。成功完成本 将使发展中必不可少的第二阶段定量重建服务得以发展， RPT的批准，并最终在精准医疗模式中提供最佳个性化给药。