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[11C]vorozole as a PET tracer for in vivo studies of human aromatase

[11C]伏唑作为人芳香酶体内研究的 PET 示踪剂

基本信息

批准号：
8217150
负责人：
ANAT BIEGON
金额：
$ 22.05万
依托单位：
BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-02-01 至 2014-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8217150
关键词：
Address Affect Alzheimer&apos s Disease Androgens Aromatase Aromatase Inhibitors Behavioral Binding Biological Assay Biological Markers Brain Brain Injuries Central Nervous System Diseases Cotinine Data Disease Dose Drug Evaluation Enzymes Estradiol Estrogens Evaluation FDA approved Future Goals Gonadal Hormones Gonadal Steroid Hormones Human Kinetics Letrozole Life Malignant neoplasm of liver Malignant neoplasm of ovary Measures Menstrual cycle Methods Modeling Monitor Names Nicotine Organ Pathology Patients Peripheral Phase Plasma Positron-Emission Tomography Proteins Public Health Radiopharmaceuticals Recruitment Activity Regulation Role Smoker Specificity Structure Testosterone Tracer Vorozole Woman age effect base cigarette smoking disease phenotype dosimetry drug development drug discovery endometriosis human disease human subject in vivo malignant breast neoplasm men non-smoker non-smoking public health relevance radiotracer tool tool development young woman

项目摘要

* DESCRIPTION (provided by applicant): Aromatase, the cyp19A gene product, is the enzyme responsible for estrogen synthesis. To date, there are no quantitative studies of the distribution and regulation of aromatase in living humans. Using a newly developed method of synthesis and purification, we propose to 1. Validate and characterize [11C]vorozole as a PET radiotracer for the non invasive assessment of aromatase in the brain and peripheral organs of living humans: This aim will address the human dosimetry, pharmacological specificity and kinetic modeling of the radiopharmaceutical. 2. Examine the effects of age, sex and gonadal hormones on the kinetic parameters of [11C]vorozole. For this aim, PET studies will be performed in men and women, young and old, and young women will be studied at different phases of the menstrual cycle. Gonadal hormone plasma levels will be assayed in all subjects. 3. Examine the effects of cigarette smoking on aromatase availability in the brain and peripheral organs. Both smokers and non-smokers will be recruited to address this aim. The data gathered from these studies will serve as the basis for an IND application, opening the way for studies using aromatase as a biomarker for drug discovery and for pathophysiological studies of CNS disorders in various pathologies. Changes in aromatase activity are implicated in a wide range of human diseases, including breast cancer, Alzheimer's disease, endometriosis, liver cancer, ovarian cancer and brain injury; which affect millions in the US. The availability of a validated tracer which can be used to detect changes in aromatase non-invasively will have a dramatic impact on the ability to select patients who can benefit from aromatase inhibitors (AI) in different diseases, facilitate AI treatment monitoring and provide a tool for new AI drug development and evaluation. PUBLIC HEALTH RELEVANCE: Changes in aromatase activity are implicated in a wide range of human diseases, including breast cancer, Alzheimer's disease, endometriosis, liver cancer and brain injury; which affect millions in the US and have a major impact on public health. The ability to use [11C]vorozole to detect changes in aromatase non-invasively will have a dramatic impact on the ability to select patients who can benefit from aromatase inhibitors, facilitate aromatase inhibitor treatment monitoring and provide a new tool for the development and evaluation of new aromatase inhibitors.

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Human Cognitive Ability Is Modulated by Aromatase Availability in the Brain in a Sex-Specific Manner.

DOI：
10.3389/fnins.2020.565668
发表时间：
2020
期刊：
Frontiers in neuroscience
影响因子：
4.3
作者：
Alia-Klein N;Preston-Campbell RN;Kim SW;Pareto D;Logan J;Wang GJ;Moeller SJ;Fowler JS;Biegon A
通讯作者：
Biegon A

In vivo visualization of aromatase in animals and humans.