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：
10116302
负责人：
John Kurhanewicz
金额：
$ 60.09万
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 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10116302
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 Individual Indolent Industrialization Industry Injections Investigation Magnetic Resonance Imaging Malignant Neoplasms Malignant neoplasm of prostate Measures Metabolic Metabolism Methods Molecular Monitor Motivation Operative Surgical Procedures Outcome Patient imaging 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 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 investigation clinical translation deprivation design first-in-human high resolution imaging human disease human imaging imaging approach imaging modality imaging study improved individual patient industry partner instrumentation meetings metabolic imaging microbial molecular imaging new technology novel novel imaging technology perfusion imaging personalized approach personalized care pre-clinical preclinical study product development prostate cancer model reconstruction research study response safety and feasibility standard of care success temporal measurement therapeutic development therapy resistant 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.

项目摘要 /摘要这种学术行业伙伴关系旨在开发和翻译新的仪器和技术 13C-rea MR灌注成像单独并与HP 13C - 丙酮酸结合使用，以实现未来的临床研究在癌症患者中，促进了一种更个性化的治疗选择和监测方法。这该项目的最终产品将是新的DDNP SpinLab偏振器硬件和能够生产的方法无菌的，超极化的化合物，用于第一组灌注和灌注和代谢成像通过初始的前列腺癌患者研究。为了完成这个重要的项目，我们已经组装了一个卓越的学术和工业团队，在临床前和临床癌症研究方面具有专业知识，惠普无菌复合，HP MRI开发和行业产品开发至：开发化学，代理商溶解DNP的硬件和方法本身用于生产无菌HP 13C-rea，然后在与无菌HP 13C-丙酮酸的结合（AIM 1）。开发和实施新颖的快速容量13C MR HP 13C-rea，13C-丙酮酸及其代谢物的串行动力成像的成像方法，高时间和空间分辨率（目标2）。 FDA IND所需的临床前测试和SOP开发提交（目标3）。建立第一组人组合HP 13C-rea和13c-的安全性和成像可行性前列腺癌患者的丙酮酸MR成像研究（AIM 4）。这种学术行业伙伴关系的临床动机是前列腺癌管理严重受当前可用的临床和成像信息的限制，以选择最合适的治疗对于个别患者，并评估对治疗或治疗耐药性的反应。超极化（HP）13C MRI是一种范式转移新的MR分子成像技术检测，表征侵略性和监测治疗以改善癌症临床试验的措施和个性化的患者护理。该项目的科学前提是，随着第1阶段的成功前列腺癌患者中HP 13C - 丙酮酸成像的临床试验，可商购的增殖临床极化器以及强大的临床前数据，证明了HP 13C尿素和丙酮酸的潜在值为了推进癌症成像，现在是将这项新技术转化为诊所并整合的时间它是当前最新成像的方法。这种学术行业伙伴关系对于强大的将这种新颖的成像技术转化为临床领域，UCSF和通用电气（GE）是独特的位置可以共同实现这一目标。尽管新型超极化成像工具和方法在这一学术中开发和传播工业伙伴关系最初将用于前列腺癌患者，他们将具有一般适用性用于各种各样的癌症和其他人类疾病。