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

摘要 这项提议的目标是使用氧化还原放大的放射性核素沉积来使非侵入性 应用正电子发射断层扫描对1型糖尿病患者的胰岛β细胞进行成像。它是 越来越清楚的是，糖尿病是一种流行病，可能是21世纪最大的健康之一 担忧。需要分子成像工具来监测疾病的进展，新的有效性 并跟踪移植细胞的存活情况。然而，尽管有这种需要，但开发一种 监测β细胞的全身分子成像技术仍然难以捉摸，主要原因是 背景信号不足，阻碍了目标稀有β细胞(约1-2%的组织)的分辨率 对抗背景胰腺细胞。在这里，我们提出了一种创新的解决方案，即PET成像放大 信号通过酶催化的放射性核素报告沉积。如果成功，此方法将表示 放射性核素成像中信号放大的一种全新方法。这种方法可能会 显著增加β细胞特异性报告器的信号输出，同时抑制 背景资料。对问题的基本分析表明，如果我们需要这样的新解决方案 希望用PET成像技术检测稀有细胞。PET信号放大通用方法的研究进展 可能导致有价值的成像工具来监测β细胞质量，并对临床产生巨大影响 1型糖尿病的诊断、治疗和了解。

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.