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Investigation of ANG II/AT1 Receptors with PET

用 PET 研究 ANG II/AT1 受体

基本信息

批准号：
8069195
负责人：
ZSOLT SZABO
金额：
$ 32.75万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-08-01 至 2013-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8069195
关键词：
Accounting Acute Address Affect Affinity Algorithms Angiotensin II Angiotensin Receptor Animal Model Animals Applications Grants Atherosclerosis Autoradiography Behavior Binding Binding Sites Biologic Characteristic Biological Markers Blood flow Canis familiaris Characteristics Clip Collimator Computational algorithm Data Deterioration Diabetes Mellitus Diagnosis Dietary Sodium Digestive System Disorders Disease Estrogens Failure Family suidae Financial compensation Funding Future Goals Grant Health Hematological Disease Human Hypertension Image Imaging Device Imaging Techniques In Vitro Investigation Kidney Kidney Diseases Kidney Part Kinetics Lead Link Measures Metabolic syndrome Methods Modeling Molecular Molecular Diagnosis Monitor Motion NIH Program Announcements Obesity Organ Patient Selection Perfusion Persons Pharmaceutical Preparations Pharmacotherapy Photons Positioning Attribute Positron Positron-Emission Tomography Predisposition Process Property Public Health Recovery Recurrence Regulation Renal Artery Stenosis Renal Blood Flow Reperfusion Therapy Research Staging Stenosis System Technology Testing Time Translations Up-Regulation Urologic Diseases Variant attenuation clinical application clinical practice density design detector image processing image reconstruction improved in vivo instrument kidney vascular structure minimally invasive molecular imaging novel pre-clinical radioligand receptor receptor binding receptor expression research study response restoration success uptake

项目摘要

DESCRIPTION (provided by applicant): During the previous funding period of this grant, several radioligands were synthesized for positron emission tomography (PET) imaging of the angiotensin II/subtype 1 receptor (AT1R). The effects of dietary sodium, estrogen, various drugs and arterial stenosis on radioligand binding in the kidneys were investigated. The results of these experiments reinforced the soundness of positron emission tomography (PET) as a state-of-the-art noninvasive imaging technique for studying the regulation of renal AT1R in vivo. Although the ultimate goal is to apply this molecular imaging tool in humans, kinetic properties of the radioligands need first be clarified in animal models. Our initial observations in dogs and pigs showed increased binding of the radioligand in renal artery stenosis. The important task remaining is to understand and quantify the distribution and kinetics of the PET radioligand in response to altered renal blood flow. To accomplish this, PET studies are proposed in dogs with and without reduced perfusion of the kidneys. The following specific aims will be addressed: Aim 1: To determine to what degree radioligand binding parameters obtained with PET studies are affected by renal blood flow. Experiments are proposed to test the hypothesis that increased in vivo radioligand binding observed in vivo correlates with in vitro quantification of the receptor in Goldblatt models of renal hypoperfusion. We also postulate that after restoration of blood flow radioligand binding will return to pre-ischemic levels. Aim 2: To apply novel quantitative PET image reconstruction and post-processing algorithms for improved receptor quantification in vivo. This aim will address the hypothesis that computational compensation for image degradation and radioligand delivery can provide receptor binding parameters largely independent of global and regional variations of organ perfusion. Integration of the preclinical experiments and the novel computational algorithms will facilitate translation of renal molecular imaging into clinical practice and lead to a rational approach for molecular diagnosis of renovascular disease. PUBLIC HEALTH RELEVANCE Kidney disease remains an important public health problem since it is closely linked to obesity, metabolic syndrome, diabetes, atherosclerosis and hypertension. The imaging techniques currently used to evaluate involvement of the kidneys rely on anatomical data. In contrast, positron emission tomography imaging (PET) makes it possible to study diseases at the molecular level. The proposed research is designed to establish PET imaging of the angiotensin receptor. In the future, this new molecular imaging tool is expected to diagnose kidney disease sooner, guide therapy, measure therapy response and detect disease recurrence or deterioration at an earlier stage.

描述（由申请人提供）：在该资助的上一个资助期内，合成了几种放射性配体，用于血管紧张素II/亚型1受体（AT 1 R）的正电子发射断层扫描（PET）成像。研究了钠、雌激素、各种药物和动脉狭窄对肾脏放射性配体结合的影响。这些实验的结果加强了正电子发射断层扫描（PET）作为一个国家的最先进的非侵入性成像技术，在体内研究肾脏AT 1 R的调节的合理性。虽然最终目标是将这种分子成像工具应用于人类，但放射性配体的动力学特性需要首先在动物模型中阐明。我们在狗和猪中的初步观察显示肾动脉狭窄中放射性配体的结合增加。剩下的重要任务是了解和量化PET放射性配体的分布和动力学对肾血流改变的反应。为了实现这一点，建议在肾脏灌注减少和未减少的犬中进行PET研究。将解决以下具体目标：目标1：确定在何种程度上放射性配体的结合参数与PET研究所获得的肾血流的影响。提出实验来检验这一假设，即在体内观察到的体内放射性配体结合增加与肾灌注不足Goldblatt模型中受体的体外定量相关。我们还推测，血流恢复后，放射性配体结合将恢复到缺血前水平。目的2：应用新的定量PET图像重建和后处理算法，以改善体内受体定量。这一目标将解决的假设，计算补偿图像退化和放射性配体输送可以提供受体结合参数，在很大程度上独立于全球和区域的变化器官灌注。临床前实验和新的计算算法的整合将有助于将肾分子成像转化为临床实践，并为肾血管疾病的分子诊断提供合理的方法。肾脏疾病仍然是一个重要的公共卫生问题，因为它与肥胖、代谢综合征、糖尿病、动脉粥样硬化和高血压密切相关。目前用于评估肾脏受累的成像技术依赖于解剖学数据。相比之下，正电子发射断层扫描成像（PET）使得在分子水平上研究疾病成为可能。该研究旨在建立血管紧张素受体的PET成像。在未来，这种新的分子成像工具有望更快地诊断肾脏疾病，指导治疗，测量治疗反应，并在早期阶段检测疾病复发或恶化。

项目成果

期刊论文数量（21）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Radiopharmaceuticals for renal positron emission tomography imaging.

DOI：
10.1053/j.semnuclmed.2007.09.008
发表时间：
2008
期刊：
Seminars in nuclear medicine
影响因子：
4.9
作者：
Z. Szabo;Jinsong Xia;W. B. Mathews
通讯作者：
Z. Szabo;Jinsong Xia;W. B. Mathews

Modeling of the renal kinetics of the AT1 receptor specific PET radioligand [11C]KR31173.

DOI：
10.1155/2013/835859
发表时间：
2013
期刊：
BioMed research international
影响因子：
0
作者：
Gulaldi NC;Xia J;Feng T;Hong K;Mathews WB;Ruben D;Kamel IR;Tsui BM;Szabo Z
通讯作者：
Szabo Z

In vivo investigation of estrogen regulation of adrenal and renal angiotensin (AT1) receptor expression by PET.

通过 PET 体内研究雌激素对肾上腺和肾血管紧张素 (AT1) 受体表达的调节。

DOI：
发表时间：
2004
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
0
作者：
Owonikoko,TaofeekK;Fabucci,MariaE;Brown,PhilipR;Nisar,Nighat;Hilton,John;Mathews,WilliamB;Ravert,HaydenT;Rauseo,Paige;Sandberg,Kathryn;Dannals,RobertF;Szabo,Zsolt
通讯作者：
Szabo,Zsolt

Model-Based receptor quantization analysis for PET parametric imaging.

基于模型的 PET 参数成像受体量化分析。