Development and Translation of Hyperpolarized C-13 Prostate Cancer MRI Methods

超极化 C-13 前列腺癌 MRI 方法的开发和转化

• 批准号: 10455772
• 负责人: Jeremy William Gordon
• 金额: $ 8.58万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10455772
• 关键词: 3-Dimensional; Acceleration; Address; Adoption; Biomedical Engineering; Biopsy; Bone Diseases; Cancer Patient; Citric Acid Cycle; Clinical; Clinical Management; Clinical Research; Clinical Trials; Collaborations; Computer software; Data; Development; Disease; Disseminated Malignant Neoplasm; Evaluation; Extramural Activities; Future; Gland; Goals; Gold; Guidelines; Histopathology; Human; Image; Imaging Techniques; Injections; Interdisciplinary Study; Intervention; Investigation; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of prostate; Measurement; Measures; Metabolic; Metabolism; Metastatic Neoplasm to Lymph Nodes; Metastatic Prostate Cancer; Methods; Monitor; Pathologic; Patient Care; Patients; Pelvis; Pharmacologic Substance; Pharmacy facility; Phase; Physiologic pulse; Positron-Emission Tomography; Predisposition; Production; Prostatectomy; Pyruvate; Pyruvate Metabolism Pathway; Reproducibility; Research; Research Personnel; Resistance; Resolution; Scientist; Site; Sterility; Structure; Techniques; Technology; Testing; Therapeutic Intervention; Time; Translating; Translations; United States National Institutes of Health; Variant; Visceral; anticancer research; base; cost effective; design; hip bone; imaging approach; imaging modality; improved; individual patient; interest; lymph nodes; metabolic imaging; molecular imaging; multi-site trial; multidisciplinary; new technology; novel; novel strategies; novel therapeutics; open source; pre-clinical; research study; response; stable isotope; success; tool; treatment response

Project Summary/Abstract This Bioengineering Research Partnership has been designed to develop new techniques to perform primary and especially metastatic prostate cancer patient HP 13C MRI exams with the goal of creating a robust, reliable exam with 2-fold higher SNR, 5-fold higher spatial coverage, and new metabolic information from C-2 pyruvate to benefit prostate cancer research, clinical trials evaluating new treatments, and ultimately patient care. Preliminary studies have demonstrated the ability of dynamic HP 13C MR to detect upregulated LDH-catalyzed pyruvate to lactate conversion in aggressive prostate cancers and also to measure a dramatic reduction following successful therapy. While “proof-of-principle” has been shown in these initial studies, new bioengineering developments, hardware, and software are required to create a robust, cost-effective HP 13C MRI exam to fulfill clinical unmet needs. The current techniques are not robust, well-characterized tools ready to be widely applied. This BRP, with its specialized multidisciplinary research team, is designed to accomplish the required bioengineering developments and patient clinical research needed to refine, test and disseminate these new techniques & hardware following the NIH guidelines for scientific rigor, transparency and reproducibility. Specifically, we aim to: 1) Improve HP Pharmacy Methods for Producing Sterile HP 13C-pyruvate; 2) Develop New Robust HP 13C MR Technology for Primary Prostate Cancer; and 3) Specific Technical Developments for Metastatic Prostate Cancer Exam. New robust acquisition and analysis techniques will be developed and tested in pre-prostatectomy patients with the correlation of kPL & kPG conversion rate constants to step-section histopathology as the gold standard. Also the new methods will be applied in studies of patients with metastases to lymph nodes and pelvic bone to investigate their ability to detect therapy response/resistance for individual patients and future clinical trials of emerging pharmaceutical strategies. While focused on prostate cancer, the proposed BRP aims to develop new HP 13C metabolic imaging techniques that will ultimately benefit the clinical management of a wide variety of diseases. All techniques, hardware designs, pharmacy methods, open-source software, and anonymized patient data from this BRP project will be disseminated to all interested sites continuing this BRP’s active dissemination methods to over 20 sites thus far in order to accelerate the tempo and improve the clinical impact of this powerful molecular imaging approach.

项目摘要/摘要 这种生物工程研究伙伴关系旨在开发新的技术来进行初步的 尤其是转移性前列腺癌患者的HP 13C MRI检查，目的是创造一个健壮、可靠的 具有2倍更高的SNR、5倍更高的空间覆盖率的检查，以及来自C-2丙酮酸的新代谢信息 以利于前列腺癌研究、临床试验评估新的治疗方法，并最终有利于患者护理。 初步研究表明，动态HP~(13)C磁共振能够检测LDH催化的上调 侵袭性前列腺癌患者丙酮酸到乳酸的转化以及下列指标的显著降低 治疗成功了。虽然在这些初步研究中已经显示出“原则证明”，但新的生物工程 需要开发、硬件和软件来创建强大、经济高效的HP 13C MRI检查以完成 临床上未得到满足的需求。目前的技术不是健壮的、特征良好的工具，没有准备好广泛应用。 该BRP及其专业的多学科研究团队旨在完成所需的 生物工程发展和患者临床研究需要提炼、测试和传播这些新的 技术和硬件遵循美国国立卫生研究院关于科学严密性、透明度和重复性的指导方针。 具体地说，我们的目标是：1)改进HP制药生产无菌HP 13C-丙酮酸的方法；2)开发 治疗原发性前列腺癌的新的强大的HP 13C磁共振技术；以及3)针对 转移性前列腺癌检查。将开发和测试新的可靠的采集和分析技术 前列腺癌患者术前KPL、KPG转换率常数与阶梯切面的相关性 以组织病理学为金标准。此外，新方法还将应用于转移患者的研究 对淋巴结和盆骨进行检测，以了解其检测个体治疗反应/耐药的能力 新兴药物策略的患者和未来临床试验。在关注前列腺癌的同时， 建议的BRP旨在开发新的HP 13C代谢成像技术，最终将使临床受益 管理各种各样的疾病。所有技术、硬件设计、药房方法、开源 软件和来自该BRP项目的匿名患者数据将传播到所有感兴趣的站点 继续这个BRP的积极传播方式，到目前为止已经超过20个站点，以加快节奏 并改善这一强大的分子成像方法的临床影响。