18F Proline Preclinical PET Imaging In The Diagnosis of Early Stage Alcoholic Liver Fibrosis

18F 脯氨酸临床前 PET 成像在早期酒精性肝纤维化诊断中的应用

• 批准号: 10223967
• 负责人: Qi Cao
• 金额: $ 19.05万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10223967
• 关键词: 3-Dimensional; Alcoholic Liver Diseases; Alcoholic steatohepatitis; Alcohols; Animal Model; Animals; Biodistribution; Biological Markers; Cell physiology; Cells; Cicatrix; Clinic; Clinical; Clinical Management; Collagen; Collagen Type I; Culture Media; Data; Desmin; Development Plans; Diagnosis; Diagnostic radiologic examination; Discipline of Nuclear Medicine; Doctor of Medicine; Doctor of Philosophy; Dose; Early Diagnosis; Early identification; Endotoxins; Enzyme-Linked Immunosorbent Assay; Enzymes; Fibroblasts; Fibrosis; Functional Imaging; Glial Fibrillary Acidic Protein; Goals; Hepatic; Hepatic Stellate Cell; Hepatocyte; Histopathology; Image; Imaging Techniques; Immunoassay; In Vitro; Inbred BALB C Mice; Investigation; Label; Link; Liquid substance; Liver; Liver Fibrosis; Liver diseases; Maryland; Measures; Mentors; Mitogen-Activated Protein Kinase Kinases; Modeling; Molecular; Morphology; Nuclear; Organ; Pathologic; Patient Care; Patients; Positron-Emission Tomography; Procedures; Procollagen; Production; Proline; Proteins; Qi; Reproducibility; Research; Research Personnel; Role; Sampling; Serology; Signal Pathway; Signal Transduction; Skeleton; Stains; System; TLR1 gene; Techniques; Technology; Time; Tissues; Tracer; Training; Translating; Universities; Vimentin; X-Ray Computed Tomography; career development; cell transformation; clinical Diagnosis; dosimetry; experimental study; feeding; global health; imaging study; in vivo; interleukin-1 receptor-associated kinase; liver injury; mRNA Expression; medical schools; molecular imaging; mouse model; noninvasive diagnosis; pre-clinical; preclinical imaging; problem drinker; professor; protein activation; radiotracer; skeletal; technique development; uptake

This K08 application is submitted by Qi Cao, M.D., Ph.D., Assistant Professor of Diagnostic Radiology and Nuclear Medicine at the University of Maryland School of Medicine. My long term goal is to become an independent investigator focusing on establishing a reliable and reproducible PET/CT technique to noninvasively and specifically diagnose early-stage alcoholic liver fibrosis (ALF). Toward this goal, I propose a mentored career development plan which provides the following training in: 1) preclinical experiments to assess specific cellular tracer uptake in vitro, 2) in new radiotracer synthesis and preclinical imaging in order to quantify biodistribution and dosimetry, and 3) in functional molecular imaging for the diagnosis of early stage liver fibrosis. SPECIFIC AIMS: The first aim is to evaluate the role of proline in collagen synthesis using 3H-labeled proline in an in vitro culture system of hepatic stellate cells (HSCs) isolated from livers of animals with alcoholic steatosis (AS), alcoholic steatohepatitis (ASH), early stage alcoholic liver fibrosis (EAF), and late stage alcoholic liver fibrosis (LAF) by using beta counting. The second aim is to establish dynamic 18F-proline PET imaging to assess radiotracer biodistribution in 12 critical organs/tissues and to optimize dosing and timing conditions which will translate this procedure to image ALF in animals with AS, ASH, EAF, and LAF as described in Aim 3. The third aim is to study the role of 18F-proline in the diagnosis of early-stage liver fibrosis in HSC from animals with AS, ASH, EAF, and LAF by static 18F-proline PET/CT imaging. The proposed complementary approaches in the specific aims will help to: (1) establish important parameters of 18F-proline labeling by optimizing tracer dosing and imaging timing conditions; and (2) determine the experimental importance of 18F-proline in the assessment of collagen production in in vitro (aim 1) and in vivo (aims 2 and 3) models, which will provide a new means to assess early liver fibrosis in patients with ALD. This line of investigation will use functional imaging to fill critical gaps in the mechanism of in vivo collagen production, which will further our understanding of liver disease and advance clinic treatment by providing a noninvasive means to diagnose early-stage liver fibrosis at a stage before damage becomes permanent. Through intensive training in the application of non-invasive molecular imaging to ALD, I will gain the expertise required of an independent investigator to apply molecular imaging to the study and diagnosis of liver disease. RELEVANCE: The project will use noninvasive 18F-proline PET/CT imaging to correlate radiotracer incorporation activity within scar formation cells with scar collagen formation. The ability to image scar formation will provide valuable data to enable the development of this technique for noninvasive identification of early-stage liver disease during routine patient care, which will greatly advance the treatment of liver disease.

本K08申请由曹琦提交，医学博士，放射诊断学助理教授

项目成果

Quantification of Hepatic Lipid Using 7.0T Proton Magnetic Resonance Spectroscopy and Computed Tomography in Mild Alcoholic Steatotic Mice.

使用 7.0T 质子磁共振波谱和计算机断层扫描对轻度酒精性脂肪变性小鼠的肝脂质进行定量。

• DOI: 10.4172/2167-0889.1000234
• 发表时间: 2018
• 期刊: Journal of liver
• 作者: Cao,Qi;Xu,Su;Li,Shujing;Chen,Minjie;Sun,Xicui;Wan,Yamin;Pi,Liya;Ying,Zhekang;Ren,Bin
• 通讯作者: Ren,Bin