Nuklearmedizin 2009; 48(01): 44-54
DOI: 10.3413/nukmed-0190
Hyperglycaemia in brain FDG PET
Schattauer GmbH

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

Insulin zur Korrektur einer hyperglykämischen Stoffwechsellage vor Hirn-FDG-PET: Computersimulationen
R. Buchert
1   Department of Nuclear Medicine; University Medical Center Hamburg-Eppendorf, Germany
,
R. Santer
2   Center of Gynaecology, Obstetrics and Paediatrics; University Medical Center Hamburg-Eppendorf, Germany
,
W. Brenner
1   Department of Nuclear Medicine; University Medical Center Hamburg-Eppendorf, Germany
,
I. Apostolova
1   Department of Nuclear Medicine; University Medical Center Hamburg-Eppendorf, Germany
,
J. Mester
1   Department of Nuclear Medicine; University Medical Center Hamburg-Eppendorf, Germany
,
M. Clausen
1   Department of Nuclear Medicine; University Medical Center Hamburg-Eppendorf, Germany
,
D. H. S. Silverman
3   Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
› Author Affiliations
Further Information

Publication History

Received: 03 June 2008

accepted in revised form: 17 January 2008

Publication Date:
19 January 2018 (online)

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.

Zusammenfassung

Ziel: Bei der FDG-PET führt eine hyperglykämische Stoffwechsellage oft zu reduzierter statistischer Bildqualität. Zur Korrektur einer hyperglykämischen Stoffwechsellage (>7,0 mmol/l) vor FDG-PET des Gehirns schlagen wir folgendes Insulin-Bolus-Protokoll vor: (i) Intravenöse Bolus-injektion kurz wirksamen Insulins, eine I.E. pro 0,6 mmol/l Blutglukose über 7,0. (ii) Kontrolle des Blutglukosespiegels 20 min nach Insulingabe. Falls weiterhin > 7,0 mmol/l, zurück zu (i), Berechnung der zusätzlichen Insulindosis mit dem aktuellen Blutglukosewert. Sonst, (iii) weitere 20 Minuten Wartezeit bis zur Injektion der FDG. (iv) sorgfältige Beobachtung des Patienten während der gesamten Untersuchung. Methode: Der Effekt des Insulin-Protokolls auf die Bildqualität bei der Hirn-FDG-PET wurde mittels Computersimulationen im Rahmen des Sokoloff-Modells abgeschätzt. Zur Plausibilitätsprüfung der vorhergesagten Effekte wurde der Zusammenhang zwischen FDG-Aufnahme des Gehirns und Blutglukosespiegel bei FDG-Injektion retrospektiv in einer Gruppe von 89 Patienten mit Verdacht auf Alzheimer-Krankheit untersucht. Ergebnisse: Nach den Computersimulationen kann die FDG-Aufnahme des Gehirns durch das vorgeschlagene Insulin-Bolus-Protokoll um bis zu 80% erhöht werden. Die Patientendaten sind in guter übereinstimmung mit einem Effekt dieser Größenordnung. Schlussfolgerung: Das Insulin-Bolus-Protokoll kann zur deutlichen Verbesserung der statistischen Bildqualität der Hirn-FDG-PET bei hyperglykämischer Stoffwechsellage führen. Eine prospektive Studie zur Validierung erscheint sinnvoll.

 
  • References

  • 1 Bartenstein P, Asenbaum S, Catafau A. et al. European Association of Nuclear Medicine procedure guidelines for brain imaging using [18F]FDG. Eur J Nucl Med Mol Imaging 2002; 29: BP43-BP48.
  • 2 Betz AL, Gilboe DD, Yudilevich DL. et al. Kinetics of unidirectional glucose transport into the isolated dog brain. Am J Physiol 1973; 225: 586-592.
  • 3 Bingham EM, Hopkins D, Smith D. et al. The role of insulin in human brain glucose metabolism: an 18Fluoro-deoxyglucose positron emission tomography study. Diabetes 2002; 51: 3384-3390.
  • 4 Brooks DJ, Gibbs JS, Sharp P. et al. Regional cerebral glucose transport in insulin-dependent diabetic patients studied using [11C]3-O-methyl-D-glucose and positron emission tomography. J Cereb Blood Flow Metab 1986; 6: 240-244.
  • 5 Buchert R, van den Hoff J, Mester J. Accurate determination of metabolic rates from dynamic positron emission tomography data with very-low temporal resolution. Journal of Computer Assisted Tomography 2003; 27: 597-605.
  • 6 Crone C. Facilitated transfer of glucose from blood into brain tissue. J Physiol 1965; 181: 103-113.
  • 7 Daniel PM, Love ER, Pratt OE. Insulin and the way the brain handles glucose. J Neurochem 1975; 25: 471-476.
  • 8 Delbeke D, Coleman RE, Guiberteau MJ. et al. Procedure guideline for tumor imaging with 18F-FDG PET/CT 1.0. J Nucl Med 2006; 47: 885-895.
  • 9 Devaskar SU, Mueckler MM. The mammalian glucose transporters. Pediatr Res 1992; 31: 1-13.
  • 10 Dreyer M, Matthaei S, Kuhnau J. et al. Prolonged plasma half-life of insulin in patients with a genetic defect of high affinity binding sites. Horm Metab Res 1986; 18: 247-249.
  • 11 Eastman RC, Carson RE, Gordon MR. et al. Brain glucose metabolism in noninsulin-dependent diabetes mellitus: a study in Pima Indians using positron emission tomography during hyperinsulinemia with euglycemic glucose clamp. J Clin Endocrinol Metab 1990; 71: 1602-1610.
  • 12 Fanelli CG, Dence CS, Markham J. et al. Blood-to-brain glucose transport and cerebral glucose metabolism are not reduced in poorly controlled type 1 diabetes. Diabetes 1998; 47: 1444-1450.
  • 13 Ferrannini E, DeFronzo RA. Insulin actions in vivo: Glucose metabolism. In: Alberti KGMM. et al. (eds) International Textbook of Diabetes Mellitus. John Wiley and Sons; 1992: 409-438.
  • 14 Gjedde A. Calculation ofcerebral glucose phosphorylation from brain uptake of glucose analogs in vivo: a re-examination. Brain Res 1982; 257: 237-274.
  • 15 Gjedde A. Does deoxyglucose uptake in the brain reflect energy metabolism?. Biochem Pharmacol 1987; 36: 1853-1861.
  • 16 Gottstein U, Held K, Sebening H. et al. Glucose consumption of the human brain under the influence of intravenous infusions of glucose, glucagon and glucose-insulin. Klin Wochenschr 1965; 43: 965-975.
  • 17 Gruetter R, Novotny EJ, Boulware SD. et al. 'H NMR studies of glucose transport in the human brain. J Cereb Blood Flow Metab 1996; 16: 427-438.
  • 18 Gruetter R, Novotny EJ, Boulware SD. et al. Direct measurement of brain glucose concentrations in humans by 13C NMR spectroscopy. Proc Natl Acad Sci USA 1992; 89: 1109-1112 12208.
  • 19 Gruetter R, Ugurbil K, Seaquist ER. Steady-state cerebral glucose concentrations and transport in the human brain. J Neurochem 1998; 70: 397-408.
  • 20 Gutniak M, Blomqvist G, Widen L. et al. D-[U-nC]glucose uptake and metabolism in the brain of insulin-dependent diabetic subjects. Am J Physiol 1990; 258: E805-E812.
  • 21 Hasselbalch SG, Knudsen GM, Videbaek C. et al. No effect of insulin on glucose blood-brain barrier transport and cerebral metabolism in humans. Diabetes 1999; 48: 1915-1921.
  • 22 Hertz MM, Paulson OB, Barry DI. et al. Insulin increases glucose transfer across the blood-brain barrier in man. J Clin Invest 1981; 67: 597-604.
  • 23 Hipszer B, Joseph J, Kam M. Pharmacokinetics of intravenous insulin delivery in humans with type 1 diabetes. Diabetes Technol Ther 2005; 7: 83-93.
  • 24 Hom FG, Goodner CJ, Berrie MA. A [3H]2-deoxyglucose method for comparing rates of glucose metabolism and insulin responses among rat tissues in vivo. Validation of the model and the absence of an insulin effect on brain. Diabetes 1984; 33: 141-152.
  • 25 Haaparanta M, Paul R, Gronroos T. et al. 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. Life Sci 2003; 73: 1437-1451.
  • 26 Lindholm P, Minn H, Leskinen-Kallio S. et al. Influence of the blood glucose concentration on FDG uptake in cancer-a PET study. J Nucl Med 1993; 34: 1-6.
  • 27 McCall AL, Gould JB, Ruderman NB. Diabetes-induced alterations of glucose metabolism in rat cerebral microvessels. Am J Physiol 1984; 247: E462-E467.
  • 28 Namba H, Lucignani G, Nehlig A. et al. Effects of insulin on hexose transport across blood-brain barrier in normoglycemia. Am J Physiol 1987; 252: E299-E303.
  • 29 Nielsen JK, Djurhuus CB, Gravholt CH. et al. Continuous glucose monitoring in interstitial subcutaneous adipose tissue and skeletal muscle reflects excursions in cerebral cortex. Diabetes 2005; 54: 1635-1639.
  • 30 Phelps ME, Huang SC, Hoffman EJ. et al. Tomographic measurement of local cerebral glucose metabolic rate in humans with (18F)2-fluoro-2-deoxy-D-glucose: validation of method. Ann Neurol 1979; 6: 371-388.
  • 31 Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 2003; 26 (Suppl 1) S5-S20.
  • 32 Sakamoto S, Ishii K, Hosaka K. et al. Detectability of hypometabolic regions in mild Alzheimer disease: function of time after the injection of 2-[fluorine 18]-fluoro-2-deoxy-D-glucose. AJNR Am J Neuroradiol 2005; 26: 843-847.
  • 33 Seaquist ER, Damberg GS, Tkac I. et al. The effect of insulin on in vivo cerebral glucose concentrations and rates of glucose transport/metabolism in humans. Diabetes 2001; 50: 2203-2209.
  • 34 Shapiro ET, Cooper M, Chen CT. et al. Change in hexose distribution volume and fractional utilization of [18F]-2-deoxy-2-fluoro-D-glucose in brain during acute hypoglycemia in humans. Diabetes 1990; 39: 175-180.
  • 35 Sokoloff L, Reivich M, Kennedy C. et al. The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 1977; 28: 897-916.
  • 36 Sperber GO. An alternative procedure for calculating glucose consumption from 2-deoxyglucose uptake. Bull Math Biol 1989; 51: 275-286.
  • 37 Tsuchida T, Sadato N, Nishizawa S. et al. Effect of postprandial hyperglycaemia in non-invasive measurement of cerebral metabolic rate of glucose in non-diabetic subjects. Eur J Nucl Med Mol Imaging 2002; 29: 248-250.
  • 38 Vitale GD, deKemp RA, Ruddy TD. et al. Myocardial glucose utilization and optimization of 18F-FDG PET imaging in patients with non-insulin-dependent diabetes mellitus, coronary artery disease, and left ventricular dysfunction. J Nucl Med 2001; 42: 1730-1736.
  • 39 Voipio-Pulkki LM, Nuutila P, Knuuti MJ. et al. Heart and skeletal muscle glucose disposal in type 2 diabetic patients as determined by positron emission tomography. J Nucl Med 1993; 34: 2064-2067.
  • 40 Waldhausl WK, Bratusch-Marrain PR, Vierhapper H. et al. Insulin pharmacokinetics following continuous infusion and bolus injection of regular porcine and human insulin in healthy man. Metabolism 1983; 32: 478-486.