PET and MR-Compatible Bioreactor for Cross-Platform Biomarker Development

用于跨平台生物标志物开发的 PET 和 MR 兼容生物反应器

• 批准号: 8520274
• 负责人: John Kurhanewicz
• 金额: $ 15.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8520274
• 关键词: Alanine; Androgens; Antiandrogen Therapy; Award; Bicarbonates; Biological Markers; Biopsy Specimen; Bioreactors; Cancer Patient; Cell Culture Techniques; Cell Line; Cells; Choline; Clinical; Companions; Culture Media; Data; Development; Dimensions; Disadvantaged; Disease; Drug Kinetics; Engineering; Environment; Evaluation; Future; Gases; Glucose; Goals; Human; Image; Imaging Techniques; In Vitro; Kinetics; Label; Literature; Magnetic Resonance Imaging; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of prostate; Measurement; Metabolic; Metabolism; Monitor; Motivation; Non-Malignant; PC3 cell line; Patients; Pharmaceutical Preparations; Pharmacodynamics; Phase I Clinical Trials; Phospholipids; Physiological Processes; Play; Positron-Emission Tomography; Prostate; Pyruvate; Radioactivity; Research; Resolution; Role; Signal Pathway; Signal Transduction; System; Technology; Testing; Therapeutic; Tissue Sample; Tissues; Tracer; Translating; Translations; VCaP; cellular imaging; clinical application; cost; cost effective; design; glucose metabolism; improved; interest; molecular imaging; novel; phosphoramidate; pre-clinical; protein function; radiotracer; rapid detection; response; screening; success; tissue culture; tissue/cell culture; treatment planning; uptake

DESCRIPTION (provided by applicant): The goal of this research is to optimize a 5mm MR-compatible PET 3D cell/tissue culture bioreactor and test it by using a combination of hyperpolarized (HP) 13C MR and PET probes. Three-dimensional (3D) cell and tissue culture bioreactors provide a novel platform to investigate, in a very controlled and cost effective environment, cell and tissue metabolism and function as well as response to therapy. Combining HP 13C labeled MR probes with MR-compatible 3D tissue culture bioreactors has allowed the monitoring of metabolic fluxes with high temporal resolution (seconds) without background signals from the culture media. The addition of positron emission tomography (PET) imaging with an array of labeled tracers provides yet another dimension to understanding metabolic function, protein interaction, signaling pathways and drug pharmacokinetics/pharmacodynamics (PK/PD), in the bioreactor system. Both hyperpolarized 13C MR and PET have advantages and disadvantages, yet there is great interest in investigating their complimentary roles in the setting of providing companion imaging biomarkers for assessing new therapies. To accomplish this we will optimize a 5mm MR-compatible PET Bioreactor (aim 1) and use this platform to investigate the synergistic role of PET and HP MR (aim 2). The test studies aim to demonstrate the breadth of application of this cross- platform bioreactor system, spanning both multinuclear PET and MR. Adapting existing micro-engineered MR compatible 3D culture bioreactor designs for PET imaging studies represents a novel direction that will have a major impact on screening and evaluation of new radiotracers and therapeutics, and in identifying the synergistic role of HP MR and PET for future clinical applications. The proposed studies will also provide new information concerning the synergistic role of MR and PET probes. This optimized 5 mm bioreactor can be further micro-engineered to allow the study of smaller amounts of primary human cells and tissues, including biopsy samples, ultimately influencing patient management.

描述（由申请人提供）：这项研究的目的是优化5mm MR兼容的PET 3D细胞/组织培养物生物反应器，并通过使用超极化（HP）13C MR和PET探针进行测试。三维（3D）细胞和组织培养物生物反应器提供了一个新的平台，以在非常有效且具有成本效益的环境，细胞和组织代谢以及功能以及对治疗的反应中研究。将标记为MR探针的HP 13C与MR兼容3D组织培养物生物反应器相结合，使得没有培养基的背景信号的具有高时间分辨率（秒）的代谢通量。在BioreACTOR系统中，添加正电子发射断层扫描（PET）成像为了解代谢功能，蛋白质相互作用，信号通路和药物药物动力学（PK/PD）提供了另一个维度。超极化的13C MR和PET都有优势和缺点，但是在研究其在提供评估新疗法的伴侣成像的环境中，他们对它们的免费角色有很大的兴趣。为此，我们将优化5mm MR兼容的PET生物反应器（AIM 1），并使用此平台研究PET和HP MR的协同作用（AIM 2）。测试研究旨在证明该跨平台生物反应器系统的应用，涵盖了多核PET和MR。适应现有的微工程MR兼容3D培养物生物反应器设计用于PET成像研究是一个新的方向，将对筛查和评估新的放射性雇用和治疗疗法以及确定HP MR和PET在未来临床应用中的协同作用产生重大影响。拟议的研究还将提供有关MR和PET探针协同作用的新信息。该优化的5 mM生物反应器可以进一步进行微工程，以允许研究少量的原代人细胞和组织，包括活检样品，最终影响患者的管理。