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

描述（由申请人提供）：本研究的目标是优化5 mm MR兼容PET 3D细胞/组织培养生物反应器，并通过使用超极化（HP）13 C MR和PET探头的组合对其进行测试。三维（3D）细胞和组织培养生物反应器提供了一个新的平台，在一个非常受控和成本效益的环境，细胞和组织的代谢和功能，以及对治疗的反应。将HP 13 C标记的MR探针与MR兼容的3D组织培养生物反应器组合，允许在没有来自培养基的背景信号的情况下以高时间分辨率（秒）监测代谢通量。添加具有标记示踪剂阵列的正电子发射断层扫描（PET）成像为理解生物反应器系统中的代谢功能、蛋白质相互作用、信号传导途径和药物药代动力学/药效学（PK/PD）提供了又一个维度。超极化13 C MR和PET都有优点和缺点，但人们对研究它们在为评估新疗法提供伴随成像生物标志物方面的互补作用非常感兴趣。为了实现这一目标，我们将优化5 mm MR兼容PET生物反应器（目的1），并使用该平台研究PET和HP MR的协同作用（目的2）。测试研究旨在证明这种跨平台生物反应器系统的应用广度，跨越多核PET和MR。将现有的微工程MR兼容3D培养生物反应器设计用于PET成像研究代表了一个新的方向，其将对新的放射性示踪剂和治疗剂的筛选和评估产生重大影响，以及在确定HP MR和PET的协同作用以用于未来的临床应用中。拟议的研究还将提供有关MR和PET探针协同作用的新信息。这种优化的5 mm生物反应器可以进一步进行微工程设计，以允许研究少量的原代人类细胞和组织，包括活检样本，最终影响患者管理。

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.