Name: determining glucose metabolism kinetics using 18f-fdg micro-pet/ct
Uploaded: 2017-05-02T14:30:00
Description: Watch this Scientific Journal Video about Determining Glucose Metabolism Kinetics Using 18F-FDG Micro-PET/CT at JoVE.com

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.

All procedures described in this study were approved by the Sydney Local Health District and University of Sydney Animal Ethics Committees and followed the NIH Guide for the care and use of laboratory animals, Eighth edition (2011).
1. Animal Preparation
NOTE: In this protocol male db/db mice (BKS.Cg-Dock7m +/+ Leprdb/J) were maintained in group housing with ad libitum access to chow and water until 6 weeks of ...

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The protocol described here represents a robust, non-invasive methodology to determine the kinetics of glucose uptake from the blood stream into tissue and subsequent metabolism in mice.
The db/db mouse is a is a well-established animal model of type 2 diabetes14 that has been used extensively to examine insulin resistance and relevant interventions. However, previous studies have only quantified endpoint uptake in the heart15 and cardiac and ske...

The purpose of this study was to develop a positron emission tomography/computed tomography (PET/CT) based methodology to quantify the in vivo, real-time uptake of glucose from the blood stream into specific tissues in mice. This was achieved using 18F-labelled fluorodeoxyglucose (FDG) to measure glucose uptake and kinetic modelling to estimate the rates of 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.
In rodents, 18F-FDG has been used in the pre-clinical assessment of numerous cancer treatments1, studies of tumor progression2 and tumor metabolism3 as well as imaging of brown fat depots4, neuroinflamation5 and brain metabolism6.
Traditional methods used to examine the tissue specific uptake of glucose in mice (and rats) generally involve treatment with 2-deoxyglucose radiolabeled with either 3H or 14C followed by euthanasia, tissue collection and measurement of radioactivity in each tissue7. The use of PET/CT allows for noninvasive determination of glucose uptake and metabolism in multiple organs and regions simultaneously in live animals. Additionally, as euthanasia is not a requirement, this technique is suitable for use in longitudinal studies.
Type 2 diabetes mellitus (T2DM) is characterized by disrupted glucose metabolism and hyperglycemia secondary to reduced tissue responsiveness to insulin (insulin resistance) and the inability of pancreatic -cells to produce adequate amounts of insulin8. Kinetic analysis of glucose uptake and metabolism can provide important insights into the mechanism of action and efficacy of therapeutic interventions as well as allow for advanced monitoring of disease progression.

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			<td height="21" style="height:21px;width:216px;">PET/CT Scanner</td>
			<td style="width:152px;">Siemens</td>
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			<td height="21" style="height:21px;width:216px;">18F-FDG</td>
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			<td height="21" style="height:21px;width:216px;">Isoflurane</td>
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			<td></td>
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		<tr height="21">
			<td height="21" style="height:21px;width:216px;">30 guage needle</td>
			<td style="width:152px;">BD</td>
			<td align="right" style="width:119px;">305106</td>
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		<tr height="21">
			<td height="21" style="height:21px;width:216px;">PMOD modelling software</td>
			<td style="width:152px;">PMOD Technologies</td>
			<td style="width:119px;"></td>
			<td></td>
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		<tr height="42">
			<td height="42" style="height:42px;width:216px;">BKS.Cg-Dock7m&#160;+/+&#160;Leprdb/J&#160; mice</td>
			<td style="width:152px;">Jackson Laboratory</td>
			<td style="width:119px;">000642</td>
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			<td height="21" style="height:21px;width:216px;">Human insulin</td>
			<td style="width:152px;">Sigma-Aldrich</td>
			<td style="width:119px;"></td>
			<td></td>
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determining glucose metabolism kinetics using 18f-fdg micro-pet/ct

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.

We have previously used the db/db mouse model to investigate the impact of increasing plasma apoA-I levels on the kinetics of glucose uptake and metabolism13. In this study we used db/db mice treated with insulin to demonstrate the utility of PET/CT imaging to monitor the uptake of 18F-FDG from the plasma into the gastrocnemius muscle in real time.
Six week old db/db mice were anesthetized and ...

Watch this Scientific Journal Video about Determining Glucose Metabolism Kinetics Using 18F-FDG Micro-PET/CT at JoVE.com

Determining Glucose Metabolism Kinetics Using 18F-FDG Micro-PET/CT

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.

Determining Glucose Metabolism Kinetics Using 18F-FDG Micro-PET/CT

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). ...

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