Microdialysis and 2-[18F]fluoro-2-deoxy-D-glucose (FDG): A study on insulin action on FDG transport, uptake and metabolism in rat muscle, liver and adipose tissue

Haaparanta, Merja; Paul, Robert; Grönroos, Tove J.; Bergman, Jörgen; Kämäräinen, Eeva-Liisa; Solin, Olof

doi:10.1016/s0024-3205(03)00470-3

Cited by 13 publications

(5 citation statements)

References 49 publications

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“…The lumped constant, which defines the ratio of [ 18 F]FDG:glucose in relation to transmembrane transport and hexokinase-mediated phosphorylation [10,11], was found to be 1.30 and 1.15 during fasting and hyperinsulinaemia, respectively. These figures are very similar to those reported in the liver [7], skeletal muscle [13] and adipose tissue [14]. Due to the limited resolution, PET images cannot differentiate the relative distribution of [ was examined by autoradiography in the mucosa and muscle layers.…”

Section: Discussionsupporting

confidence: 83%

Validation of [18F]fluorodeoxyglucose and positron emission tomography (PET) for the measurement of intestinal metabolism in pigs, and evidence of intestinal insulin resistance in patients with morbid obesity

et al. 2013

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Aims/hypothesis The role of the intestine in the pathogenesis of metabolic diseases is gaining much attention. We therefore sought to validate, using an animal model, the use of positron emission tomography (PET) in the estimation of intestinal glucose uptake (GU), and thereafter to test whether intestinal insulin-stimulated GU is altered in morbidly obese compared with healthy human participants. Methods In the validation study, pigs were imaged using In the clinical study, GU was measured in different regions of the intestine in lean (n=8) and morbidly obese (n=8) humans at baseline and during euglycaemic hyperinsulinaemia.

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Section: Discussionsupporting

confidence: 83%

Validation of [18F]fluorodeoxyglucose and positron emission tomography (PET) for the measurement of intestinal metabolism in pigs, and evidence of intestinal insulin resistance in patients with morbid obesity

et al. 2013

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“…The glucose analogue [ 18 F]fluoro-deoxyglucose (FDG) is trapped in living tissues as a function of the local rate of glucose consumption; this property has made FDG the most widely-used tracer for clinical molecular imaging studies of oncology and disorders of brain metabolism. High resolution positron emission tomography with dedicated instruments for small animals (μPET) has presented new possibilities for measuring the rate of glucose consumption in diverse experimental models (Toyama et al 2003, Haaparanta et al 2003, Bergman et al 1994, Gronroos et al 1998, Kreissl et al 2004, 2006, Shimoji et al 2004, Toyama 2005, Cunningham et al 2004. Absolute quantitation of FDG uptake generally entails serial sampling of arterial blood, so as to derive the FDG input function.…”

Section: Introductionmentioning

confidence: 99%

Noninvasive image derived heart input function for CMRglc measurements in small animal slow infusion FDG PET studies

Xiong

Cumming²,

Todica³

et al. 2012

Phys. Med. Biol.

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Absolute quantitation of the cerebral metabolic rate for glucose (CMRglc) can be obtained in positron emission tomography (PET) studies when serial measurements of the arterial [(18)F]-fluoro-deoxyglucose (FDG) input are available. Since this is not always practical in PET studies of rodents, there has been considerable interest in defining an image-derived input function (IDIF) by placing a volume of interest (VOI) within the left ventricle of the heart. However, spill-in arising from trapping of FDG in the myocardium often leads to progressive contamination of the IDIF, which propagates to underestimation of the magnitude of CMRglc. We therefore developed a novel, non-invasive method for correcting the IDIF without scaling to a blood sample. To this end, we first obtained serial arterial samples and dynamic FDG-PET data of the head and heart in a group of eight anaesthetized rats. We fitted a bi-exponential function to the serial measurements of the IDIF, and then used the linear graphical Gjedde-Patlak method to describe the accumulation in myocardium. We next estimated the magnitude of myocardial spill-in reaching the left ventricle VOI by assuming a Gaussian point-spread function, and corrected the measured IDIF for this estimated spill-in. Finally, we calculated parametric maps of CMRglc using the corrected IDIF, and for the sake of comparison, relative to serial blood sampling from the femoral artery. The uncorrected IDIF resulted in 20% underestimation of the magnitude of CMRglc relative to the gold standard arterial input method. However, there was no bias with the corrected IDIF, which was robust to the variable extent of myocardial tracer uptake, such that there was a very high correlation between individual CMRglc measurements using the corrected IDIF with gold-standard arterial input results. Based on simulation, we furthermore find that electrocardiogram-gating, i.e. ECG-gating is not necessary for IDIF quantitation using our approach.

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“…As a consequence, hyperinsulin aemia results in increased peripheral FDG plasma clearance due to insulin-induced increase of FDG uptake by muscle and adipose tissue. Haaparanta et al, using microdialysis, found that in rats the elimination half-life of FDG from blood decreased by about 60% after a bolus injection of insulin, independent of the nutritional status of the rats (fasting or fed) (25 cose at the glucose transporters of the blood-brain barrier due to increased clearance of glucose into peripheral tissues, versus increased clearance of FDG itself from the plasma into peripheral tissues. Thus, the ability to improve image quality through use of insulin will depend upon maximizing the effect of insulin on endogenous glucose, relative to its effect on exogenous FDG.…”

Section: Insulin Zur Korrektur Einer Hyper Glykämischen Stoffwechsellmentioning

confidence: 99%

Computer simulations suggest that acute correction of hyperglycaemia with an insulin bolus protocol might be useful in brain FDG PET

Buchert¹,

Santer²,

Brenner³

et al. 2009

Nuklearmedizin

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Summary Aim: FDG PET in hyperglycaemic subjects often suffers from limited statistical image quality, which may hamper visual and quantitative evaluation. In our study the following insulin bolus protocol is proposed for acute correction of hyperglycaemia (> 7.0 mmol/l) in brain FDG PET. (i) Intravenous bolus injection of short-acting insulin, one I.E. for each 0.6 mmol/l blood glucose above 7.0. (ii) If 20 min after insulin administration plasma glucose is ≤ 7.0 mmol/l, proceed to (iii). If insulin has not taken sufficient effect step back to (i). Compute insulin dose with the updated blood glucose level. (iii) Wait further 20 min before injection of FDG. (iv) Continuous supervision of the patient during the whole scanning procedure. Methods: The potential of this protocol for improvement of image quality in brain FDG PET in hyperglycaemic subjects was evaluated by computer simulations within the Sokoloff model. A plausibility check of the prediction of the computer simulations on the magnitude of the effect that might be achieved by correction of hyperglycaemia was performed by retrospective evaluation of the relation between blood glucose level and brain FDG uptake in 89 subjects in whom FDG PET had been performed for diagnosis of Alzheimer's disease. Results: The computer simulations suggested that acute correction of hyperglycaemia according to the proposed bolus insulin protocol might increase the FDG uptake of the brain by up to 80%. The magnitude of this effect was confirmed by the patient data. Conclusion: The proposed management protocol for acute correction of hyper glycaemia with insulin has the potential to significantly improve the statistical quality of brain FDG PET images. This should be confirmed in a prospective study in patients.

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Microdialysis and 2-[18F]fluoro-2-deoxy-D-glucose (FDG): A study on insulin action on FDG transport, uptake and metabolism in rat muscle, liver and adipose tissue

Cited by 13 publications

References 49 publications

Validation of [18F]fluorodeoxyglucose and positron emission tomography (PET) for the measurement of intestinal metabolism in pigs, and evidence of intestinal insulin resistance in patients with morbid obesity

Validation of [18F]fluorodeoxyglucose and positron emission tomography (PET) for the measurement of intestinal metabolism in pigs, and evidence of intestinal insulin resistance in patients with morbid obesity

Noninvasive image derived heart input function for CMRglc measurements in small animal slow infusion FDG PET studies

Computer simulations suggest that acute correction of hyperglycaemia with an insulin bolus protocol might be useful in brain FDG PET

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