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

项目摘要 癌症、心血管疾病和糖尿病等疾病的细胞病理生理学， 早在疾病症状出现之前就开始改变了。此外，目前的成像技术 通常仅可视化形态和结构。因此，可以表征代谢的成像技术 变化有可能在疾病症状明显之前很久就发现疾病过程。 因此，代谢和功能成像允许更早的诊断和治疗。体内代谢成像， 它区分了构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机制。目前的代谢成像技术， 例如PET和SPECT，由于使用了 放射性造影剂。因此，这些技术的广泛临床应用范围有限。在 临床前模型，其他技术，如用于质谱分析的处死动物的组织切片， 需要用于研究细胞代谢，导致临床前和临床前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颖的易于操作的工具， 造影剂能够实现无创、节省成本和可重复的体内临床前成像， 临床翻译该工具制备可用作注射造影剂的超极化代谢物 常规MRI系统可见的药剂。超极化代谢物，如[1- 13 C]-丙酮酸， 信号增强的自旋，并可以在真实的时间跟踪和报告代谢转化和途径。 Vizma的工具可以很容易地适应广泛使用的动物设施和纵向研究中，在同一个 动物，从而减少实验变异性和所需的动物数量，因为动物不需要 为了代谢成像而牺牲该工具将直接改善动物研究向临床的转化 验证。本阶段I SBIR的总体目标是使Vizma超极化过程完全 生物相容性。这涉及从基于醇的超极化过程中调整[1- 13 C]-丙酮酸盐超极化过程。 溶液到水溶液，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 在动物体内用化学位移成像检测水溶液的急性注射和监测 另一组动物每周一次接受水溶液的超极化注射，持续两周。 成功完成第I阶段SBIR将导致体内概念验证并支持第II阶段 研究其在成像多个物种的疾病的多个动物模型中的用途。的最终目标 该项目旨在将该技术商业化，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.