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.

项目摘要 基础疾病的细胞病理生理学，例如癌症，心血管疾病和糖尿病， 在疾病症状显而易见之前开始改变。而且，当前的成像技术 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发音之前很长时间检测疾病过程。 因此，代谢成像和功能成像允许更早的诊断和治疗。体内代谢成像， 可以区分构成细胞过程的化学反应的变化，可用于改善 了解疾病发作和进展的基础机制。当前的代谢成像技术， 例如宠物和SPECT，由于使用而不得 放射性对比剂。因此，这些技术的广泛临床利用在范围上受到限制。在 临床前模型，其他技术，例如牺牲动物的组织切片进行质谱分析， 需要用来研究细胞代谢，从而导致临床前的翻译差距很大 动物模型和临床研究。 Vizma Life Sciences开发了一种新颖的易于操作的工具来准备 对比造影剂，可以在体内临床前成像中实现无创，节省成本和可重复的对比剂 进行临床翻译。该工具准备了可用作可注射对比度的超极化代谢物 常规MRI系统可见的代理。超极化的代谢产物，例如[1-13c] - 丙酮酸，具有 信号增强的自旋，可以实时跟踪并报告代谢转换和途径。 Vizma的工具可以很容易地适应动物设施和纵向研究中的广泛使用 动物，从而减少了实验变异性和动物不需要的动物数量 为代谢成像而牺牲。该工具将直接改善动物研究对临床的翻译 验证。该阶段I SBIR的总体目标是使Vizma超极化过程完全 生物相容性。这涉及从基于酒精的[1-13c] - 丙酮酸超极化过程 溶液到水溶液中，确定灵敏度极限，然后测量残留溶液和催化剂 污染。通过评估该技术的体内可行性和安全性 检测在动物中用化学偏移成像的水溶液急性注射并进行监测 另一组动物每周一次接受一次性水溶液的超极化注射两周。 成功完成此阶段I SBIR将导致体内概念验证和支持II阶段 研究其在多种物种中成像多种疾病模型中的使用。最终目标 该项目是将这项技术商业化，以在临床前和临床环境中进行广泛使用。