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

项目摘要/摘要 这一学术和行业合作伙伴关系旨在为惠普开发和翻译新仪器和技术 13C-尿素磁共振灌注成像单独以及与HP 13C-丙酮酸联合使用以进行未来的临床研究 这有助于以更个性化的方式进行治疗选择和监测。这个 该项目的最终产品将是新的DDNP SpinLab偏振器硬件和方法，能够生产 无菌超极化化合物用于首次人灌注和联合灌注和代谢成像 通过对前列腺癌患者的初步调查。为了完成这一重要项目，我们召集了 惠普是一支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 无菌合成、HP MRI开发和工业产品开发：开发化学、试剂 自行生产无菌HP~(13)C-尿素的溶解DNP的硬件和方法 联合无菌幽门螺杆菌13C-丙酮酸(目标1)。新型快速容量~(13)C磁共振的研制 HP~(13)C-尿素、~(13)C-丙酮酸及其代谢物系列动态成像的成像方法 时间和空间分辨率(目标2)。FDA IND所需的临床前测试和SOP开发 意见书(目标3)。建立首例人用HP 13C-尿素和13C-尿素联合应用的安全性和成像可行性 前列腺癌患者的丙酮酸磁共振成像研究(目标4)。 这种学术和产业合作的临床动机是前列腺癌的治疗严重。 受限于当前可用的临床和影像信息，需要选择最合适的治疗方案 以评估对治疗的反应或治疗抵抗的发展。 超极化(HP)13C磁共振是一种改变范式的新MR分子成像技术，它提供了新的 为改进癌症临床试验而采取的检测、表征侵袭性和监测治疗的措施 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 幽门螺杆菌13C-丙酮酸显像在前列腺癌患者临床试验中的应用 临床偏振剂和强有力的临床前数据表明HP 13C尿素和丙酮酸的潜在价值 为了推进癌症成像，现在正是将这项新技术转化为临床并整合 将其转化为当前最先进的成像方法。这种学术和产业的伙伴关系对于强健的 将这一新的成像技术转化为临床领域，加州大学旧金山分校和通用电气(GE) 独一无二的地位，可以共同实现这一目标。 尽管在这一学术领域开发和传播的新型超极化成像工具和方法- 产业伙伴关系将首先应用于前列腺癌患者，它们将具有普遍的适用性 治疗多种癌症和其他人类疾病。

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.