确定葡萄糖代谢动力学研究<sup> 18</sup> F-FDG微PET / CT
Summary
This study describes a protocol that uses 18F-FDG and positron emission tomography/computed tomography (PET/CT) imaging, together with kinetic modelling, to quantify the in vivo, real-time uptake of 18F-FDG into tissues.
Abstract
This paper describes the use of 18F-FDG and micro-PET/CT imaging to determine in vivo glucose metabolism kinetics in mice (and is transferable to rats). Impaired uptake and metabolism of glucose in multiple organ systems due to insulin resistance is a hallmark of type 2 diabetes. The ability of this technique to extract an image-derived input function from the vena cava using an iterative deconvolution method eliminates the requirement of the collection of arterial blood samples. Fitting of tissue and vena cava time activity curves to a two-tissue, three compartment model permits the estimation of kinetic micro-parameters related to the 18F-FDG uptake from the plasma to the intracellular space, the rate of transport from intracellular space to plasma and the rate of 18F-FDG phosphorylation. This methodology allows for multiple measures of glucose uptake and metabolism kinetics in the context of longitudinal studies and also provides insights into the efficacy of therapeutic interventions.
Introduction
本研究的目的是开发一种正电子发射断层成像/计算机断层扫描（PET / CT）为基础的方法从血液流入小鼠特定组织量化葡萄糖的体内 ，实时摄取。这是使用18 F-标记的氟代脱氧葡萄糖（FDG），以测量葡萄糖摄取和动力学模型来估计18 F-FDG摄取的速率从等离子体到细胞内空间，交通的速率从细胞内空间到等离子体和的速率来实现18 F-FDG的磷酸化。
在啮齿动物中，18 F-FDG已经在许多癌症治疗1，肿瘤进展2和肿瘤代谢3的研究以及褐色脂肪库4，neuroinflamation 5和脑代谢6的成像的临床前评估中使用</SUP>。
用于检查葡萄糖小鼠（和大鼠）的组织特异性摄取通常涉及与任一3 H或14 C，随后安乐死，组织收集和测量放射性每个组织7的2-脱氧葡萄糖的放射性标记的治疗传统的方法。使用PET / CT的允许在多个器官和地区非侵入性的决心葡萄糖的吸收和代谢的同时在活的动物。另外，如安乐死不是必需的，该技术是适合于在纵向研究中使用。
2型糖尿病（T2DM）的特征在于破坏葡萄糖代谢和高血糖症继发于降低组织响应性胰岛素（胰岛素抵抗）和胰腺β-细胞的不能产生足够量的胰岛素8。葡萄糖摄取和代谢动力学分析可以提供重要的见解动作和治疗性干预的功效的机制以及允许疾病进展的先进的监控。
Protocol
Representative Results
Discussion
这里描述的协议代表一个健壮的，非侵入性的方法来从血流进入组织以及随后的代谢在小鼠中测定的葡萄糖摄取的动力学。
所述的db / db小鼠是是已经广泛用于检查胰岛素抗性和相关的干预2型糖尿病14的公认动物模型。然而，以往的研究只量化端点摄取的心脏15和心脏和骨骼肌16。
利用动力学分析以确?…
Offenlegungen
The authors have nothing to disclose.
Acknowledgements
This work was supported by a National Imaging Facility Subsidised Access Grant to BJC, a National Health and Medical Research Council of Australia program grant (482800) to KAR and PJB. The authors would like to thank Andrew Arthur, Hasar Hazme and Marie-Claude Gregoire for support in developing this method.
Materials
| PET/CT Scanner | Siemens | Inveon | |
| 18F-FDG | PETNET Solutions | ||
| Isoflurane | Pharmachem | ||
| 30 guage needle | BD | 305106 | |
| PMOD modelling software | PMOD Technologies | ||
| BKS.Cg-Dock7m +/+ Leprdb/J mice | Jackson Laboratory | 000642 | |
| Human insulin | Sigma-Aldrich |
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