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Hyperpolarized 13C Probes for Imaging Warburg Metabolism in Cancer

用于癌症 Warburg 代谢成像的超极化 13C 探针

基本信息

批准号：
10206185
负责人：
Kelvin L Billingsley
金额：
$ 31.95万
依托单位：
CALIFORNIA STATE UNIVERSITY FULLERTON
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10206185
关键词：
Biochemical Pathway Biology Biomedical Research California Cancer Model Carbon Cell Survival Cells Cellular biology Characteristics Chemicals Chemistry Citric Acid Cycle Clinical Clinical Research Clinical Trials Communities Deuterium Development Diagnosis Diagnostic Dihydroxyacetone Disease Elements Emerging Technologies Evaluation Fumarates Funding Glyceraldehyde Glycolysis Goals H1299 In Vitro Individual Investigation Isotope Labeling Label Libraries Magnetic Resonance Magnetic Resonance Spectroscopy Malignant - descriptor Malignant Neoplasms Malignant neoplasm of lung Malignant neoplasm of prostate Measurement Medical Imaging Medicine Metabolic Metabolic Pathway Metabolism Methods Molecular Probes Molecular Structure Monitor NMR Spectroscopy Noise Onset of illness Oxidative Phosphorylation Partition Coefficient Pathway interactions Pharmacotherapy Positioning Attribute Property Pyruvate Relaxation Reporting Research Sampling Signal Transduction Solubility Structure Students Succinates Techniques Technology Time Tissues Toxic effect Underrepresented Minority Universities Warburg Effect Work analog cancer cell cancer diagnosis cancer imaging chemical property chemical synthesis clinical application clinical investigation design imaging agent imaging probe improved in vivo insight lung xenograft metabolic imaging metabolic profile minority student molecular imaging mouse model novel physical property programs research clinical testing scaffold spectroscopic survey targeted agent tool tumor tumor metabolism uptake

项目摘要

Project Summary/Abstract. Although medical imaging has become an essential component in cancer diagnosis, many traditional technologies remain inadequate at early stages of disease onset or with localized tumors. The objective of this work is the development of hyperpolarized 13C imaging agents that effectively provide insight into the metabolic profile of tumors and thereby provide a novel clinical tool to identify malignant tissues. These chemical probes will target a hallmark of cancer metabolism known as the Warburg effect, where an increase in glycolytic activity and a decrease in oxidative phosphorylation via the tricarboxylic acid cycle are observed. Novel libraries of 13C-labeled molecular probes will be prepared in order to optimize their physical and chemical properties for clinical investigations. These agents will be employed in hyperpolarized 13C magnetic resonance spectroscopic studies using both in vitro and in vivo cancer models to identify ideal candidates for cancer imaging. These hyperpolarized 13C probes will therefore provide novel methods for cancer diagnosis and offer new opportunities for monitoring distinctive aspects of tumor metabolism, which is of broad importance to a range of scientific and biomedical communities.

项目摘要/摘要。尽管医学成像已经成为癌症诊断的重要组成部分，但许多传统技术在疾病发病的早期阶段或在本地化的情况下仍然不足肿瘤。这项工作的目标是开发超极化13C显像剂有效地洞察肿瘤的代谢概况，从而提供一种新的用于识别恶性组织的临床工具。这些化学探针将瞄准癌症的一个标志。新陈代谢被称为沃堡效应，其中糖酵解活性的增加和通过三羧酸循环观察到氧化磷酸化的减少。小说将制备13C标记分子探针库，以优化其物理和化学性能用于临床研究的化学性质。这些试剂将被用于超极化利用体外和体内癌症模型进行~(13)C磁共振波谱研究确定癌症成像的理想候选者。因此，这些超极化的13C探测器将为癌症诊断提供新的方法，为监测提供新的机会肿瘤代谢的独特方面，这对一系列科学研究具有广泛的重要性和生物医学社区。