Bestemmelse glucosemetabolisme Kinetics Brug<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
Formålet med denne undersøgelse var at udvikle en positronemissionstomografi / computertomografi (PET / CT) metode til at kvantificere in vivo, realtid optagelse af glucose fra blodet ind i specifikke væv i mus. Dette blev opnået ved anvendelse af 18F-mærket fluordeoxyglucose (FDG) til at måle glucoseoptagelse og kinetisk modellering for at estimere satserne for 18F-FDG-optagelse fra plasmaet til det intracellulære rum, transporthastigheden fra intracellulære rum til plasma og hastigheden af 18F-FDG phosphorylering.
Hos gnavere er 18F-FDG blevet anvendt i præ-kliniske vurdering af talrige kræftbehandling 1, undersøgelser på tumorudvikling 2 og tumor metabolisme 3 samt billeddannelse af brune fedtdepoter 4, neuroinflamation 5 og hjerne stofskifte 6 </sup>.
Traditionelle metoder til at undersøge den vævsspecifikke optagelse af glucose i mus (og rotter) involverer generelt behandling med 2-deoxyglucose radioaktivt mærket med enten 3H eller 14C efterfulgt af eutanasi, væv indsamling og måling af radioaktivitet i hvert væv 7. Anvendelsen af PET / CT muliggør ikke-invasiv bestemmelse af glucoseoptagelse og metabolisme i flere organer og regioner samtidigt i levende dyr. Derudover, som eutanasi er ikke et krav, denne teknik er egnet til anvendelse i longitudinelle undersøgelser.
Type 2-diabetes mellitus (T2DM) er kendetegnet ved forstyrret glucosemetabolisme og hyperglykæmi sekundær til reduceret væv respons på insulin (insulinresistens) og den manglende evne af pancreas-celler til at producere tilstrækkelige mængder insulin 8. Kinetisk analyse af glukoseoptagelse og stofskifte kan give vigtig indsigt ivirkningsmekanismen og effekten af terapeutiske interventioner samt give mulighed for avanceret overvågning af sygdomsprogression.
Protocol
Representative Results
Discussion
Protokollen beskrevet her repræsenterer en robust, ikke-invasiv metode til at bestemme kinetikken af glucoseoptagelse fra blodstrømmen i væv og efterfølgende metabolisme i mus.
Db / db-mus er en er en veletableret dyremodel for type 2-diabetes 14, der er blevet anvendt i vid udstrækning til at undersøge insulinresistens og relevante indsatser. Imidlertid har tidligere undersøgelser kun kvantificeret endpoint optagelse i hjertet 15 …
Divulgazioni
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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