Novel Hyperpolarized Agents for the Metabolic Imaging of Cancer

用于癌症代谢成像的新型超极化剂

基本信息

批准号：
9538082
负责人：
Kelvin L Billingsley
金额：
$ 14万
依托单位：
CALIFORNIA STATE UNIVERSITY FULLERTON
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-17 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9538082
关键词：
Acids Animal Model Biological Biology Biomedical Research Cancerous Carbon Carboxylic Acids Cell Survival Cell membrane Cell model Cells Characteristics Chemicals Chemistry Citric Acid Cycle Clinical Clinical Trials Elements Energy Metabolism Environment Enzymes Evaluation Exhibits Formulation Foundations Fumarates Funding Glycolysis Goals Human Hydrolysis Hypoxia Individual Investigation LNCaP Label Magnetic Resonance Spectroscopy Malignant - descriptor Malignant Neoplasms Mediating Medical Imaging Medicine Metabolic Metabolism Methods Mitochondria Modification Molecular Probes Molecular Structure Monitor NMR Spectroscopy New Agents Noise Nuclear Oxidative Phosphorylation PC3 cell line Partition Coefficient Permeability Pharmaceutical Chemistry Process Production Property Pyruvate Relaxation Research Sampling San Francisco Series Signal Transduction Students Succinates Technology Time Tissues Toxic effect Transmembrane Transport Tricarboxylic Acids Universities Warburg Effect analog base cancer cell cancer imaging chemical property chemical synthesis clinical application design esterase experimental study functional group imaging agent imaging probe in vivo innovation insight interest metabolic imaging metabolic profile mitochondrial metabolism molecular imaging mouse model novel physical property preclinical evaluation programs prostate cancer cell line prostate cancer model public health relevance transgenic adenocarcinoma of mouse prostate tumor tumor metabolism underrepresented minority student uptake

项目摘要

DESCRIPTION (provided by applicant): We aim to develop molecular imaging agents for hyperpolarized 13C magnetic resonance spectroscopy (MRS) that effectively access the intracellular environment of malignant tissue and provide insight into the metabolic profile of tumors. A series of 13C-labeled analogs of tricarboxylic cycle intermediates, which exhibit enhanced cell permeability and are effectively metabolized, will be explored. Through chemical synthesis, systematic modification of carboxylic acid functional groups will yield the corresponding biologically cleavable carboxyl moieties and provide probes with the desired properties. These agents will be assessed to determine ideal candidates and subsequently be employed in hyperpolarized 13C MRS studies of tricarboxylic acid cycle metabolism in cellular and animal models of prostate cancer. New strategies for molecular probe delivery in hyperpolarized 13C MR spectroscopy will offer unique opportunities for targeting specific aspects of tumor metabolism, which will be of broad importance to medicinal chemistry, chemical biology, and medical imaging.

描述（由适用提供）：我们旨在开发用于超极化13C磁共振光谱（MRS）的分子成像剂，该磁共振光谱（MRS）有效地进入恶性组织的细胞内环境，并洞悉肿瘤的代谢特征。将探索一系列13C标记的三核周期中间体的类似物，这些类似物暴露了增强的细胞渗透性并有效地代谢。通过化学合成，羧酸官能团的系统修饰将产生相应的生物学上可裂解的羧基部分，并提供所需特性的问题。将评估这些药物以确定理想的候选物，然后在前列腺癌的细胞和动物模型中对超极化13C MRS研究进行了超极化13C MRS研究。超极化13C MR光谱法分子探针递送的新策略将为靶向肿瘤代谢的特定方面提供独特的机会，这对医学化学，化学生物学和医学成像至关重要。