Amplifying PET Imaging Signals for In Vivo Detection of Pancreatic Beta-cells

放大 PET 成像信号用于体内检测胰腺 β 细胞

• 批准号: 9760875
• 负责人: Neal Krishna Devaraj
• 金额: $ 8.18万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-25 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9760875
• 关键词: Beta Cell; Biology; Cell Transplants; Cells; Deposition; Detection; Development; Diabetes Mellitus; Disease; Disease Progression; Effectiveness; Enzymes; Epidemic; Generic Drugs; Health; Image; Imaging Device; Imaging Techniques; Insulin; Insulin-Dependent Diabetes Mellitus; Lead; Methods; Monitor; Output; Oxidation-Reduction; Pancreas; Positron-Emission Tomography; Radioisotopes; Radionuclide Imaging; Reporter; Resolution; Signal Transduction; Structure of beta Cell of islet; Tissues; clinical Diagnosis; diabetic patient; improved; in vivo; innovation; molecular imaging; non-invasive imaging; novel; novel strategies; novel therapeutics; prevent; tool; type I diabetic

Abstract The objective of this proposal is to use redox amplified radionuclide deposition to enable the non-invasive imaging of pancreatic beta-cells in type 1 diabetic patients using positron emission tomography (PET). It is becoming increasingly clear that diabetes is an epidemic and may be one of the 21st century's greatest health concerns. Molecular imaging tools are needed to monitor the progression of disease, the effectiveness of novel therapeutics, and to track the viability of transplanted cells. However, despite this need, the development of a whole-body molecular imaging technique to monitor beta-cells has remained elusive primarily due to inadequate signal-to-background, which prevents the resolution of target rare beta-cells (~1-2% of tissue) against background pancreatic cells. Here we propose an innovative solution, the amplification of PET imaging signals through enzyme catalyzed radionuclide reporter deposition. If successful, this method would represent a fundamentally new approach to signal amplification in radionuclide imaging. Such methods could dramatically increase signal output from beta-cell specific reporters while simultaneously suppressing background. A fundamental analysis of the problem suggests that such novel solutions are a requirement if we hope to detect rare cells using PET imaging. The development of generic methods to amplify PET signals could lead to valuable imaging tools for monitoring beta-cell mass and have an enormous impact on the clinical diagnosis, treatment, and understanding of type 1 diabetes.

摘要

项目成果

Laccase-Mediated Catalyzed Fluorescent Reporter Deposition for Live-Cell Imaging.

• DOI: 10.1002/cbic.201900593
• 发表时间: 2020-01-15
• 期刊: Chembiochem : a European journal of chemical biology
• 作者: Cisneros BT;Devaraj NK
• 通讯作者: Devaraj NK

Lipase mimetic cyclodextrins.

脂肪酶模拟循环克罗斯特林。

• DOI: 10.1039/d0sc05711h
• 发表时间: 2020-11-19
• 期刊: Chemical science
• 影响因子: 8.4
• 作者: Lee Y;Devaraj NK
• 通讯作者: Devaraj NK