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

非侵入性分子成像工具，用于快速纵向评估动物研究和护理中的局部代谢紊乱

• 批准号: 10602045
• 负责人: Carlos Dedesma
• 金额: $ 27.46万
• 依托单位: VIZMA LIFE SCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10602045
• 关键词: Acute; Adopted; Alcohols; Animal Disease Models; Animal Experimentation; Animal Model; Animals; Biochemical; Biological Sciences; Cardiovascular Diseases; Cell physiology; Chemical Shift Imaging; Chemicals; Clinic; Clinical; Clinical Research; Complex; Contrast Media; Cost Savings; Dedications; Detection; Diabetes Mellitus; Diagnosis; Disease; Disease Progression; Disease model; Early Diagnosis; Early treatment; Euthanasia; Filtration; Functional Imaging; Functional disorder; Goals; Heart Diseases; Image; Imaging Device; Imaging Techniques; Infrastructure; Injectable; Injections; Intravenous; Investigation; Laboratory Animal Production and Facilities; Licensing; Longevity; Longitudinal Studies; Magnetic Resonance Imaging; Malignant Neoplasms; Mass Spectrum Analysis; Measurement; Measures; Metabolic; Metabolic Pathway; Metabolism; Methods; Molecular; Monitor; Morphology; NMR Spectroscopy; Onset of illness; Organ; Pathway interactions; Phase; Positron-Emission Tomography; Pre-Clinical Model; Precipitation; Preparation; Process; Pyruvate; Radioactive; Radioactivity; Reporting; Residual state; Rodent; Safety; Signal Transduction; Slice; Small Business Innovation Research Grant; Solvents; Structure; Study models; Symptoms; System; Techniques; Technology; Time; Tissues; Toxic effect; Translating; Translations; Validation; Visualization; Weight; Wistar Rats; Work; animal care; animal facility; animal safety; aqueous; biomaterial compatibility; catalyst; cellular imaging; chemical reaction; clinical practice; clinical translation; commercialization; cost; data modeling; detection limit; imaging modality; improved; in vivo; in vivo imaging; insight; longitudinal animal study; metabolic imaging; molecular imaging; non-invasive imaging; novel; pre-clinical; pre-clinical research; preclinical imaging; prevent; safety and feasibility; single photon emission computed tomography; skills; success; tool

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.

项目概要 癌症、心血管疾病和糖尿病等疾病的细胞病理生理学， 此外，在疾病症状变得明显之前很久就开始发生变化。 通常只能可视化形态和结构，因此，成像技术可以表征代谢。 变化有可能早在疾病症状明显之前就发现疾病进程。 因此，代谢和功能成像可以更早地诊断和治疗体内代谢成像。 它区分构成细胞过程的化学反应的变化，可用于更好地 了解当前的代谢成像技术的潜在机制， PET 和 SPECT 等技术昂贵、困难，并且由于使用 因此，这些技术的广泛临床应用范围受到限制。 临床前模型、其他技术，例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，导致临床前研究之间存在非常大的转化差距 Vizma Life Sciences 开发了一种新颖的易于操作的准备工具。 造影剂能够实现无创、节省成本、可重复的体内临床前成像，并且易于使用 该工具可制备可用作注射造影剂的超极化代谢物。 传统 MRI 系统可见的超极化代谢物，例如 [1-13C]-丙酮酸盐，具有 信号增强的旋转，可以实时跟踪并报告代谢转化和途径。 Vizma 的工具可以轻松适应在动物设施和同一领域的纵向研究中的广泛使用。 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 该工具将直接促进动物研究向临床的转化。 第一阶段 SBIR 的总体目标是使 Vizma 超极化过程完全实现。 这涉及调整基于酒精的[1-13C]-丙酮酸超极化过程。 溶解成水溶液，确定灵敏度极限，然后测量残留溶剂和催化剂 将通过评估污染水平来检查该技术的体内可行性和安全性。 利用化学位移成像对动物中水溶液的急性注射进行检测和监测 另一组动物每周接受一次超极化水溶液注射，持续两周。 第一阶段 SBIR 的成功完成将带来体内概念验证并支持第二阶段 其最终目标是研究其在多个物种的多种疾病动物模型中的应用。 该项目旨在将该技术商业化，广泛应用于临床前和临床环境。