用于癌症代谢成像的新型超极化剂-猫眼课题宝

用于癌症代谢成像的新型超极化剂

批准号：

8854604

负责人：

Kelvin L Billingsley

金额：

$15.4万

依托单位：

SAN FRANCISCO STATE UNIVERSITY

依托单位国家：

美国

项目类别：

财政年份：

2015

资助国家：

美国

项目状态：

已结题

起止时间：

2015-07-07 至 2018-06-30

来源：

https://reporter.nih.gov/project-details/8854604

关键词：

Acids Animal Model Biology Biomedical Research Cancerous Carbon Carboxylic Acids Cell Survival Cell membrane Cell model Cells Characteristics Chemicals Chemistry Citric Acid Cycle Clinical Clinical Trials Drug Formulations Elements Energy Metabolism Environment Enzymes Evaluation Exhibits Foundations Fumarates Funding Glycolysis Goals Human Hydrolysis Hypoxia Image Individual Investigation LNCaP Label Magnetic Resonance Spectroscopy Malignant - descriptor Malignant Neoplasms Malignant neoplasm of prostate 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 functional group imaging agent imaging probe in vivo innovation insight interest molecular imaging mouse model novel physical property preclinical evaluation programs prostate cancer cell line prostate cancer model public health relevance research study transgenic adenocarcinoma of mouse prostate tumor tumor metabolism underrepresented minority student uptake

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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.

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