Het bepalen van glucosemetabolisme Kinetics Met behulp<sup> 18</sup> F-FDG Micro-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
Het doel van deze studie was een positron emissie tomografie / computertomografie (PET / CT) gebaseerde methodologie voor de in vivo, real-time opname van glucose kwantificering van de bloedstroom in specifieke weefsels in muizen ontwikkelen. Dit werd bereikt met 18F gemerkte fluordeoxyglucose (FDG) tot glucoseopname en kinetische modellering meten om de snelheden van 18F-FDG opname schatten uit het plasma naar de intracellulaire ruimte, de transportsnelheid van intracellulaire ruimte plasma en het percentage 18F-FDG fosforylering.
In knaagdieren is 18F-FDG gebruikt in de pre-klinische evaluatie van talrijke kankerbehandelingen 1, studies van tumorprogressie 2 en tumormetabolisme 3 en afbeelden van bruin vet depots 4, neuroinflamation 5 en 6 hersenenmetabolisme </sup>.
Traditionele methoden voor het weefsel specifieke opname van glucose in muizen (en ratten) onderzoeken omvatten in het algemeen een behandeling met 2-deoxyglucose radioactief gemerkt met hetzij 3H of 14C gevolgd door euthanasie, inzameling weefsels en meting van de radioactiviteit in elk weefsel 7. Het gebruik van PET / CT maakt een niet-invasieve bepaling van glucoseopname en metabolisme in meerdere organen en gebieden gelijktijdig in levende dieren. Bovendien euthanasie is geen vereiste, deze techniek is geschikt voor toepassing in longitudinale studies.
Type 2 diabetes mellitus (T2DM) wordt gekenmerkt door verstoord glucosemetabolisme en hyperglykemie door een verminderde weefsel gevoeligheid voor insuline (insulineresistentie) en het onvermogen van pancreas-cellen om voldoende hoeveelheden insuline produceren 8. Kinetische analyse van de opname van glucose en metabolisme kunnen belangrijke inzichten in te verstrekkenhet werkingsmechanisme en de werkzaamheid van therapeutische interventies en zorgen voor geavanceerde monitoring van ziekteprogressie.
Protocol
Representative Results
Discussion
De hier beschreven protocol vormt een robuuste, niet-invasieve methode om de kinetiek van glucoseopname bepalen uit de bloedstroom in het weefsel, waarna metabolisme in muizen.
De db / db muis is een is een gevestigde diermodel van type 2 diabetes 14 die uitgebreid heeft gebruikt om insulineresistentie en relevante interventies te onderzoeken. Echter, eerdere studies hebben alleen gekwantificeerd eindpunt opname in het hart 15 en hart- en skele…
Disclosures
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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