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

项目概要/摘要 该生物工程研究伙伴关系旨在开发新技术， 尤其是转移性前列腺癌患者HP 13 C MRI检查，其目的是创建一个强大的，可靠的 SNR提高2倍，空间覆盖率提高5倍，并从C-2丙酮酸中获得新的代谢信息 有益于前列腺癌研究、评估新治疗方法的临床试验，以及最终的患者护理。 初步研究表明，动态HP 13 C MR能够检测LDH催化的上调。 在侵袭性前列腺癌中，丙酮酸转化为乳酸，并且还测量了 成功的治疗虽然“原理证明”已经在这些初步研究中显示，新的生物工程 需要开发硬件和软件来创建一个强大的、具有成本效益的HP 13 C MRI检查， 未满足的临床需求。目前的技术并不强大，良好的特点的工具，准备广泛应用。 该BRP及其专业的多学科研究团队旨在完成所需的 生物工程的发展和病人的临床研究需要完善，测试和传播这些新的 技术和硬件遵循NIH的科学严谨性，透明度和可重复性指南。 具体而言，我们的目标是：1）改进生产无菌HP 13 C-丙酮酸盐的HP制药方法; 2）开发 用于原发性前列腺癌的新的强大HP 13 C MR技术;以及3）针对以下方面的特定技术开发： 转移性前列腺癌检查。新的强大的采集和分析技术将被开发和测试 术前kPL和kPG转化速率常数与阶梯切除的相关性 组织病理学作为金标准。新方法也将应用于转移瘤患者的研究 淋巴结和骨盆骨，以研究其检测个体治疗反应/抗性的能力。 患者和未来的临床试验的新兴制药策略。在关注前列腺癌的同时， 拟议的BRP旨在开发新的HP 13 C代谢成像技术，最终将有利于临床 管理各种疾病。所有技术、硬件设计、制药方法、开源 软件和来自该BRP项目的匿名患者数据将分发给所有感兴趣的网站 继续这一BRP的积极传播方法，到目前为止，已超过20个地点，以加快克里思 并提高这种强大的分子成像方法的临床效果。

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.