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CLINICAL TRANSLATION OF HYPERPOLARIZED 13C-UREA FOR CANCER MR MOLECULAR IMAGING

超极化 13C-尿素用于癌症 MR 分子成像的临床转化

基本信息

批准号：
9291096
负责人：
Marcus Ferrone
金额：
$ 68.46万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-03-06 至 2022-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9291096
关键词：
2,4-Dinitrophenol Address Advanced Malignant Neoplasm Androgens Biopsy Cancer Patient Chemistry Clinic Clinical Clinical Data Clinical Management Clinical Research Clinical Trials Data Development Diagnosis Disease Dose Endotoxins Evaluation Feasibility Studies Formulation Frequencies Future Gland Goals Human Hypoxia Image Imaging Device Imaging Techniques Imaging technology Individual Indolent Industrialization Industry Injectable Injection of therapeutic agent Investigation Magnetic Resonance Imaging Malignant Neoplasms Malignant neoplasm of prostate Measures Metabolic Metabolism Methods Molecular Monitor Motivation Operative Surgical Procedures Outcome Patients Performance Perfusion Pharmacy facility Phase I Clinical Trials Positioning Attribute Pre-Clinical Model Preclinical Testing Procedures Process Production Pyruvate Quality Control Radiation therapy Radical Prostatectomy Resistance development Resolution Safety Site Standardization Sterility Techniques Testing Therapeutic Time Transgenic Organisms Translating Translations Urea advanced disease anticancer research base cancer clinical trial cancer genomics cancer imaging clinical imaging clinical investigation clinical translation deprivation design high resolution imaging human disease human imaging imaging approach imaging modality imaging study improved individual patient industry partner instrumentation man meetings metabolic imaging microbial molecular imaging new technology novel perfusion imaging personalized approach personalized care pre-clinical preclinical study product development prostate cancer model reconstruction research clinical testing research study response safety and feasibility standard of care success temporal measurement therapeutic development tool treatment response tumor metabolism

项目摘要

PROJECT SUMMARY / ABSTRACT This Academic-Industry partnership aims to develop and translate new instrumentation and techniques for HP 13C-urea MR perfusion imaging alone and in combination with HP 13C-pyruvate to enable future clinical studies of patients with cancer, facilitating a more personalized approach to therapeutic selection and monitoring. The end product of this project will be new dDNP Spinlab polarizer hardware and methods capable of producing sterile, hyperpolarized compounds for first-in-man perfusion and combined perfusion and metabolic imaging through initial prostate cancer patient investigations. To accomplish this important project, we have assembled an exceptional academic and industrial team with expertise in pre-clinical and clinical cancer research, HP sterile compounding, HP MRI development, and industry product development to: Develop chemistry, agent hardware and methods of dissolution DNP for the production of sterile HP 13C-urea by itself and then in combination with sterile HP 13C-pyruvate (Aim 1). Develop and implement novel rapid volumetric 13C MR imaging methods for serial dynamic imaging of HP 13C-urea, 13C-pyruvate and its metabolites, with high temporal and spatial resolution (Aim 2). Preclinical Testing and SOP development required for FDA IND submission (Aim 3). Establish safety and imaging feasibility of first-in-man combined HP 13C-urea and 13C- pyruvate MR imaging studies in patients with prostate cancer (Aim 4). The clinical motivation for this academic-industry partnership is that prostate cancer management is severely limited by currently available clinical and imaging information required to select the most appropriate treatment for individual patients and to assess response to therapy or development of therapeutic resistance. Hyperpolarized (HP) 13C MRI is a paradigm shifting new MR molecular imaging technique that provides new measures to detect, characterize aggressiveness, and monitor therapy in order to improve cancer clinical trials and individualized patient care. The scientific premise for this project is that, with the success of phase 1 clinical trial of HP 13C-pyruvate imaging in prostate cancer patients, the proliferation of commercially available clinical polarizers, and the strong pre-clinical data demonstrating the potential value of HP 13C urea & pyruvate for advancing cancer imaging, the time is right for translating this new technology into the clinic and integrating it into current state-of-the-art imaging approaches. This Academic-Industry partnership is critical for robustly translating this novel imaging technology into the clinical arena, and UCSF and General Electric (GE) are uniquely positioned to accomplish this goal together. Although the novel hyperpolarized imaging tools and methods developed and disseminated in this academic- industrial partnership will initially be applied to patients with prostate cancer, they will have general applicability for a wide variety of cancers, and other human diseases.

项目总结/摘要这种学术界与工业界的合作旨在为惠普开发和转化新的仪器和技术单独使用13 C-尿素MR灌注成像以及与HP 13 C-丙酮酸盐联合使用，以支持未来的临床研究癌症患者，促进更个性化的治疗选择和监测方法。的该项目的最终产品将是新的dDNP Spinlab偏振器硬件和方法能够产生用于首次人体灌注和组合灌注与代谢成像的无菌超极化化合物通过对前列腺癌患者的初步调查。为了完成这个重要的项目，我们已经聚集了惠普是一个在临床前和临床癌症研究方面拥有专业知识的杰出学术和工业团队，无菌混合、HP MRI开发和工业产品开发，以：开发化学、试剂溶解DNP的硬件和方法，用于单独生产无菌HP 13 C-尿素，然后在与无菌HP 13 C-丙酮酸盐组合（Aim 1）。开发和实施新型快速容积13 C MR HP 13 C-尿素、13 C-丙酮酸及其代谢物的连续动态成像的成像方法，时间和空间分辨率（目标2）。FDA IND所需的临床前试验和SOP开发提交（目标3）。确定首次人体联合HP 13 C-尿素和13 C-尿素的安全性和成像可行性。前列腺癌患者的丙酮酸盐MR成像研究（目的4）。这种学术-工业合作的临床动机是，前列腺癌的管理是严重的，受当前可用的临床和影像学信息的限制，需要选择最合适的治疗方法并评估对治疗的反应或治疗抗性的发展。超极化（HP）13 C MRI是一种范式转变的新MR分子成像技术，检测、表征侵袭性和监测治疗的措施，以改善癌症临床试验和个性化的病人护理。这个项目的科学前提是，随着第一阶段的成功，在前列腺癌患者中进行HP 13 C-丙酮酸盐成像的临床试验，临床偏光镜，以及证明HP 13 C尿素和丙酮酸盐潜在价值的强有力的临床前数据为了推进癌症成像，现在是将这项新技术转化为临床并整合到将其转化为当前最先进的成像方法。这种学术界与工业界的伙伴关系对于将这种新的成像技术转化为临床竞技场，UCSF和通用电气（GE）正在共同实现这一目标的独特优势。虽然新的超极化成像工具和方法的发展和传播，在这个学术- 工业伙伴关系将首先应用于前列腺癌患者，它们将具有普遍适用性治疗各种癌症和其他人类疾病。