Non-invasive molecular imaging tool for rapid, longitudinal assessment of localized metabolic disruptions in animal research and care

项目总结 疾病背后的细胞病理生理学，如癌症、心血管疾病和糖尿病， 早在疾病症状变得明显之前就开始发生变化。此外，目前的成像技术 通常只可视化形态和结构。因此，能够表征新陈代谢的成像技术 变化有可能在疾病症状出现之前很久就发现疾病过程。 因此，代谢和功能成像可以更早地进行诊断和治疗。体内代谢成像， 它可以区分组成细胞过程的化学反应的变化，可以用来更好地 了解疾病发生和发展的潜在机制。目前的代谢成像技术， 如PET和SPECT，昂贵、困难，而且由于使用 放射性造影剂。因此，这些技术的广泛临床应用在范围上是有限的。在……里面 临床前模型，其他技术，如用于质谱分析的牺牲动物的组织切片， 需要用来研究细胞新陈代谢，导致临床前阶段之间存在非常大的翻译差距 动物模型和临床研究。Vizma生命科学公司开发了一种新的易于操作的工具来准备 造影剂能够实现非侵入性、节省成本和可重复的体内临床前成像，并且是可服从的 到临床翻译。该工具制备了可用作注射对比剂的超极化代谢物 常规核磁共振系统可见的代理。超极化的代谢物，如[1-13C]-丙酮酸， 信号增强的自旋，可以实时跟踪并报告代谢变化和途径。 Vizma的工具可以很容易地在动物设施中广泛使用，并在相同的纵向研究中使用 动物，从而减少了实验的可变性和动物不需要的动物数量 作为代谢成像的牺牲品。这一工具将直接促进动物研究向临床的转化 验证。此第一阶段SBIR的总体目标是使Vizma超极化过程完全 生物相容。这涉及到从基于酒精的[1-13C]-丙酮酸超极化过程 水溶液，确定灵敏度极限，然后测量残留溶剂和催化剂 污染。该技术的体内可行性和安全性将通过评估 动物急性注射水溶液的化学位移成像检测及监测 另一组动物每周接受一次超极化水溶液注射，持续两周。 成功完成这一第一阶段SBIR将导致体内概念验证和支持第二阶段 研究其在成像多种物种疾病的多种动物模型中的应用。的最终目标是 该项目旨在将这项技术商业化，以便在临床前和临床环境中广泛使用。

PROJECT SUMMARY The cellular pathophysiology that underlies diseases, such as cancer, cardiovascular disease, and diabetes, begins to change long before disease symptoms become apparent. Moreover, current imaging techniques typically only visualize morphology and structure. Therefore, imaging techniques that can characterize metabolic changes have the potential to detect disease processes long before disease symptoms are pronounced. Metabolic and functional imaging thus allows much earlier diagnosis and treatment. In vivo metabolic imaging, which distinguishes changes in the chemical reactions that make up cellular processes, can be used to better understand the mechanisms underlying disease onset and progression. Current metabolic imaging techniques, such as PET and SPECT, are expensive, difficult, and not conducive for longitudinal studies due to the use of radioactive contrast agents. Therefore, the broad clinical utilization of these techniques is limited in scope. In preclinical models, other techniques, such as tissue slicing of sacrificed animals for mass spectrometry analysis, need to be employed to study cellular metabolism, resulting in a very large translational gap between preclinical animal models and clinical studies. Vizma Life Sciences has developed a novel easy-to-operate tool to prepare contrast agents that enable noninvasive, cost-saving, and repeatable in vivo preclinical imaging and is amenable to clinical translation. The tool prepares hyperpolarized metabolites that can be used as injectable contrast agents visible to conventional MRI systems. The hyperpolarized metabolites, such as [1-13C]-pyruvate, have signal-boosted spins and can be tracked in real time and report on metabolic transformations and pathways. Vizma’s tool can be easily adapted for broad use in animal facilities and in longitudinal studies in the same animals, thus reducing experimental variability and the number of animals required as the animals do not need to be sacrificed for metabolic imaging. This tool will directly improve the translation of animal research to clinical validation. The overall goal of this Phase I SBIR is to make the Vizma hyperpolarization process fully biocompatible. This involves adapting the [1-13C]-pyruvate hyperpolarization process from an alcohol-based solution to an aqueous solution, determining sensitivity limits, and then measuring residual solvent and catalyst contamination. The in vivo feasibility and safety of the technology will be examined by assessing the levels of detection of acute injections of the aqueous solution with chemical shift imaging in animals and monitoring another set of animals receiving hyperpolarized injections of the aqueous solution once a week for two weeks. Successful completion of this Phase I SBIR will result in in vivo proof-of-concept and support Phase II investigations of its use in imaging multiple animal models of disease in multiple species. The ultimate goal of this project is to commercialize this technology for broad use in preclinical and clinical settings.