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: 10588591
• 负责人: Jeremy William Gordon
• 金额: $ 3.82万
• 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/10588591
• 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.

项目概要/摘要 该生物工程研究合作伙伴关系旨在开发新技术来执行初级研究 特别是转移性前列腺癌患者 HP 13C MRI 检查，目的是创建强大、可靠的 检查的信噪比提高了 2 倍，空间覆盖范围提高了 5 倍，并且还提供了来自 C-2 丙酮酸的新代谢信息 有益于前列腺癌研究、评估新疗法的临床试验以及最终的患者护理。 初步研究表明动态 HP 13C MR 能够检测上调的 LDH 催化 侵袭性前列腺癌中丙酮酸向乳酸的转化，还可以测量以下情况的显着减少 虽然这些初步研究已经证明了“原理验证”，但新的生物工程已经取得了成功。 创建强大、经济高效的 HP 13C MRI 检查需要开发、硬件和软件来满足 目前的技术还不是可以广泛应用的强大、特性良好的工具。 该 BRP 及其专业的多学科研究团队旨在实现所需的目标 需要生物工程的发展和患者临床研究来完善、测试和传播这些新的 技术和硬件遵循 NIH 科学严谨性、透明度和可重复性指南。 具体来说，我们的目标是： 1) 改进 HP Pharmacy 生产无菌 HP 13C-丙酮酸盐的方法 2) 开发； 针对原发性前列腺癌的新型稳健 HP 13C MR 技术；以及 3) 针对原发性前列腺癌的具体技术开发 将开发和测试新的强大的采集和分析技术。 在前列腺切除术前患者中，kPL 和 kPG 转换率常数与阶梯段的相关性 组织病理学作为金标准，新方法也将应用于转移患者的研究。 淋巴结和骨盆骨，以研究它们检测个体治疗反应/耐药性的能力 患者和新兴药物策略的未来临床试验在关注前列腺癌的同时， 拟议的 BRP 旨在开发新的 HP 13C 代谢成像技术，最终使临床受益 所有技术、硬件设计、药学方法、开源。 该 BRP 项目的软件和匿名患者数据将传播到所有感兴趣的站点 继续该 BRP 的主动传播方式，目前已覆盖 20 多个站点，以加快速度 并提高这种强大的分子成像方法的临床影响。