Co-Clinical Quantitative Imaging of Small Cell Neuroendocrine Prostate Cancer Using Hyperpolarized 13C MRI

使用超极化 13C MRI 对小细胞神经内分泌前列腺癌进行临床联合定量成像

基本信息

批准号：
10669081
负责人：
John Kurhanewicz
金额：
$ 65.68万
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：
2020
资助国家：
美国
起止时间：
2020-09-07 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10669081
关键词：
2,4-Dinitrophenol Address Androgen Receptor Androgens Basic Science Biological Markers Biology Biopsy Blood Tests Bone Diseases Cancer Detection Carboplatin Clinical Clinical Investigator Clinical Management Clinical Protocols Clinical Research Clinical Trials Communities Consensus Data Data Analyses Disease Echo-Planar Imaging Elements Event Funding Generations Genetic Goals Grant Heterogeneity Image Imaging Device Imaging Techniques Informatics Information Resources Liver Liver diseases Magnetic Resonance Magnetic Resonance Imaging Malignant Neoplasms Malignant neoplasm of prostate Measurement Metabolic Metastatic Neoplasm to the Bone Metastatic Neoplasm to the Liver Metastatic Prostate Cancer Methods Modeling Molecular Mus Neoplasm Metastasis Neuroendocrine Cell Neuroendocrine Prostate Cancer Neuroendocrine Tumors Neurosecretory Systems Noise Oncology Outcome Pathologic Pathway interactions Patients Physiologic pulse Platinum Positron-Emission Tomography Prediction of Response to Therapy Process Protocols documentation Pyruvate Receptor Signaling Reproducibility Research Research Design Research Project Grants Resistance Resources Serum Signal Transduction Site Somatostatin Receptor Technology Testing Therapeutic Clinical Trial Treatment Efficacy United States National Institutes of Health Validation advanced prostate cancer analytical tool androgen deprivation therapy anticancer research bone cancer clinical trial castration resistant prostate cancer chemotherapy clinical imaging co-clinical trial conventional therapy data acquisition data modeling data repository data standards fluorodeoxyglucose imaging approach imaging informatics imaging modality imaging study improved improved outcome in vivo informatics infrastructure inhibitor men metabolic imaging metabolic profile mouse model new therapeutic target next generation novel online repository online resource patient derived xenograft model patient response pre-clinical preclinical development predictive marker programs quantitative imaging radio frequency real time monitoring response response biomarker stable isotope standard of care temporal measurement therapy resistant tool transcriptomics transdifferentiation translational barrier treatment response tumor xenograft web portal

项目摘要

PROJECT SUMMARY / ABSTRACT The goal of this Oncology Co-Clinical Imaging Research Program (CIRP) proposal is to overcome the translational barrier, as stated in PAR-18-184, to develop co-clinical imaging research resources that will encourage a consensus on how quantitative imaging methods are optimized to improve the quality of imaging results for co-clinical trials. This will be accomplished by using novel quantitative metabolic preclinical hyperpolarized (HP) 13C magnetic resonance imaging (MRI) to assess therapeutic response of small cell neuroendocrine (SCNC) prostate cancer (PCa). The murine imaging study will be conducted in parallel to a clinical trial (NCI R01 CA215694), aiming to assess response of SCNC to carboplatin in men with metastatic PCa, led by Drs. John Kurhanewicz and Rahul Aggarwal at UCSF. SCNC is an increasingly prevalent, lethal subtype of PCa that arises as an adaptive response to the application of androgen deprivation therapy and second-generation potent androgen pathway inhibitors. The selection of the most appropriate treatment of patients with metastatic SCNC is hindered by the fact that neither blood tests or current imaging modalities can reliably identify therapeutic efficacy in these metastatic tumors which are also often not amenable to biopsy. The study design of this U24 project incorporates the four key elements of CIRP: 1) The preclinical development and optimization of quantitative HP 13C MRI acquisition and data analysis methods that address the lack in rigor and reproducibility of existing preclinical and clinical approaches (aim 1); 2) The use of appropriate patient-derived xenograft (PDX) models that reflect the genetic, metabolic and micro-environmental heterogeneity of SCNC metastases in patients; 3) The application of the optimized preclinical dynamic HP 13C MRI protocols and data modeling approaches to study the response of metastatic bone and liver disease in the PDX models to chemotherapy, paralleling the funded study in patients (aim 2); and 4) The establishment of an online resource of quantitative HP 13C MRI imaging protocols, data analyses, modeling tools, correlative biology data for wider dissemination, validation and establishment of consensus by the scientific community (aim 3). To accomplish this important translational quantitative imaging project, we have assembled an exceptional team of basic science and clinical investigators with complimentary expertise in preclinical and clinical cancer research, realistic PDX models, HP 13C MRI, informatics, and in leading imaging and therapeutic clinical trials. This research project will also capitalize on the extensive resources provided by the NIH funded P41 Hyperpolarized Magnetic Resonance Technology Resource Center, the large number of preclinical and clinical DNP polarizers and 13C-enabled MRI scanners, and imaging informatics infrastructure which exist at UCSF. Although this proposal will focus on current standard of care treatment, the new quantitative HP 13C metabolic MRI approaches developed in this proposal will have general applicability for a variety of new targeted therapeutic approaches being developed for SCNC as well as for the study of other diseases.

项目概要/摘要该肿瘤联合临床影像研究计划 (CIRP) 提案的目标是克服转化障碍，如 PAR-18-184 中所述，开发临床联合影像研究资源，鼓励就如何优化定量成像方法以提高成像质量达成共识联合临床试验的结果。这将通过使用新型定量代谢临床前技术来实现超极化 (HP) 13C 磁共振成像 (MRI) 评估小细胞的治疗反应神经内分泌癌 (SCNC) 前列腺癌 (PCa)。小鼠成像研究将与临床试验（NCI R01 CA215694），旨在评估男性转移性 SCNC 对卡铂的反应 PCa，由博士领导。加州大学旧金山分校的约翰·库哈内维奇 (John Kurhanewicz) 和拉胡尔·阿加瓦尔 (Rahul Aggarwal)。 SCNC 是一种日益普遍、致命的疾病 PCa 亚型是对雄激素剥夺疗法应用的适应性反应而出现的第二代强效雄激素途径抑制剂。选择最合适的治疗方案血液检测或当前的影像学检查都无法对转移性 SCNC 患者进行诊断可靠地确定这些转移性肿瘤的治疗效果，这些肿瘤通常也不适合活检。这该 U24 项目的研究设计纳入了 CIRP 的四个关键要素：1）临床前开发和优化定量 HP 13C MRI 采集和数据分析方法，解决缺乏严谨性和现有临床前和临床方法的可重复性（目标 1）； 2) 使用适当的源自患者的反映SCNC遗传、代谢和微环境异质性的异种移植（PDX）模型患者体内发生转移； 3）优化的临床前动态HP 13C MRI协议和数据的应用研究 PDX 模型中转移性骨和肝病的反应的建模方法化疗，与资助的患者研究并行（目标 2）； 4）建立在线资源定量 HP 13C MRI 成像协议、数据分析、建模工具、相关生物学数据，可用于更广泛的研究科学界的传播、验证和达成共识（目标 3）。为了完成这一重要的转化定量成像项目，我们组建了一支出色的团队具有临床前和临床癌症专业知识的基础科学和临床研究人员研究、真实 PDX 模型、HP 13C MRI、信息学以及领先的成像和治疗临床试验。该研究项目还将利用 NIH 资助的 P41 提供的广泛资源超极化磁共振技术资源中心，大量临床前及临床 UCSF 拥有 DNP 偏振器和支持 13C 的 MRI 扫描仪以及成像信息学基础设施。尽管该提案将重点关注当前的护理治疗标准，但新的定量 HP 13C 代谢本提案中开发的 MRI 方法将普遍适用于各种新的目标正在为 SCNC 以及其他疾病的研究开发治疗方法。