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

摘要 该提案的目的是使用氧化还原放大放射性核素沉积， 使用正电子发射断层扫描（PET）对1型糖尿病患者的胰腺β细胞进行成像。是 越来越清楚的是，糖尿病是一种流行病，可能是21世纪世纪最大的健康问题之一， 性问题需要分子成像工具来监测疾病的进展，新的药物治疗的有效性， 治疗，并跟踪移植细胞的活力。然而，尽管有这种需要， 监测β细胞的全身分子成像技术仍然难以捉摸，主要是由于 信号与背景的比值不足，导致无法分辨目标罕见β细胞（约1-2%的组织） 对照背景胰腺细胞。在这里，我们提出了一个创新的解决方案，PET成像的放大 通过酶催化的放射性核素报告沉积的信号。如果成功，这种方法将代表 放射性核素成像中信号放大的一种全新方法。此类方法可 显著增加来自β细胞特异性报告物的信号输出，同时抑制 背景对问题的基本分析表明，如果我们 希望能用PET成像检测稀有细胞。PET信号放大通用方法的开发 可能导致有价值的成像工具，用于监测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.