Intravenous regular insulin is an efficient and safe procedure for obtaining high-quality cardiac 18F-FDG PET images: an open-label, single-center, randomized controlled prospective trial



An open-label, single-center, randomized controlled prospective trial was performed to assess the efficiency and safety of an insulin loading procedure to obtain high-quality cardiac 18F-FDG PET/CT images for patients with coronary artery disease (CAD).


Between November 22, 2018 and August 15, 2019, 60 patients with CAD scheduled for cardiac 18F-FDG PET/CT imaging in our department were randomly allocated in a 1:1 ratio to receive an insulin or standardized glucose loading procedure for cardiac 18F-FDG imaging. The primary outcome was the ratio of interpretable images (high-quality images defined as myocardium-to-liver ratios ≥ 1). The secondary outcome was the patient preparation time (time interval between administration of insulin/glucose and 18F-FDG injection). Hypoglycemia events were recorded.


The ratio of interpretable cardiac PET images in the insulin loading group surpassed the glucose loading group (30/30 vs. 25/30, P = 0.026). Preparation time was 71±2 min shorter for the insulin loading group than for the glucose loading group (P < 0.01). Two and six hypoglycemia cases occurred in the insulin and glucose loading groups, respectively.


The insulin loading protocol was a quicker, more efficient, and safer preparation for gaining high-quality cardiac 18F-FDG images.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3



Coronary artery disease




Positron emission tomography


Ssingle photon emission computerized tomography


Blood glucose


Glucose transporter 4


Volume of interest


Standardized uptake value


  1. 1.

    Dilsizian V, Bacharach SL, Beanlands RS, Bergmann SR, Delbeke D, Dorbala S, et al. ASNC imaging guidelines/SNMMI procedure standard for positron emission tomography (PET) nuclear cardiology procedures. J Nucl Cardiol. 2016;23:1187–226.

    Article  Google Scholar 

  2. 2.

    Panza JA, Ellis AM, Al-Khalidi HR, Holly TA, Berman DS, Oh JK, et al. Myocardial viability and long-term outcomes in ischemic cardiomyopathy. N Engl J Med. 2019;381:739–48.

    Article  Google Scholar 

  3. 3.

    Ling LF, Marwick TH, Flores DR, Jaber WA, Brunken RC, Cerqueira MD, et al. Identification of therapeutic benefit from revascularization in patients with left ventricular systolic dysfunction: inducible ischemia versus hibernating myocardium. Circ Cardiovasc Imaging. 2013;6:363–72.

    Article  Google Scholar 

  4. 4.

    Anavekar NS, Chareonthaitawee P, Narula J, Gersh BJ. Revascularization in patients with severe left ventricular dysfunction: is the assessment of viability still viable? J Am Coll Cardiol. 2016;67:2874–87.

    Article  Google Scholar 

  5. 5.

    Valentin RC, Farag A, Hage FG, Bhambhvani P. Non-diagnostic 18F-FDG PET myocardial viability studies in type-2 diabetic patients. J Nucl Cardiol. 2019;26(5):1775–6.

    Article  Google Scholar 

  6. 6.

    Gibb AA, Hill BG. Metabolic coordination of physiological and pathological cardiac remodeling. Circ Res. 2018;123:107–28.

    CAS  Article  Google Scholar 

  7. 7.

    Fazakerley DJ, Lawrence SP, Lizunov VA, Cushman SW, Holman GD. A common trafficking route for GLUT4 in cardiomyocytes in response to insulin, contraction and energy-status signalling. J Cell Sci. 2009;122:727–34.

    CAS  Article  Google Scholar 

  8. 8.

    Leto D, Saltiel AR. Regulation of glucose transport by insulin: traffic control of GLUT4. Nat Rev Mol Cell Biol. 2012;13:383–96.

    CAS  Article  Google Scholar 

  9. 9.

    Jaldin-Fincati JR, Pavarotti M, Frendo-Cumbo S, Bilan PJ, Klip A. Update on GLUT4 vesicle traffic: a cornerstone of insulin action. Trends Endocrinol Metab. 2017;28:597–611.

    CAS  Article  Google Scholar 

  10. 10.

    Zhu Y, Pereira RO, O’Neill BT, Riehle C, Ilkun O, Wende AR, et al. Cardiac PI3K-Akt impairs insulin-stimulated glucose uptake independent of mTORC1 and GLUT4 translocation. Mol Endocrinol. 2013;27:172–84.

    CAS  Article  Google Scholar 

  11. 11.

    Chareonthaitawee P, Gersh BJ, Araoz PA, Gibbons RJ. Revascularization in severe left ventricular dysfunction: the role of viability testing. J Am Coll Cardiol. 2005;46:567–74.

    Article  Google Scholar 

  12. 12.

    American Diabetes Association. 6. glycemic targets: standards of medical care in diabetes-2018. Diabetes Care. 2018;41:S55–64.

    Article  Google Scholar 

  13. 13.

    Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50:122S–50S.

    CAS  Article  Google Scholar 

  14. 14.

    Markendorf S, Benz DC, Messerli M, Grossmann M, Giannopoulos AA, Patriki D, et al. Value of 12-lead electrocardiogram to predict myocardial scar on FDG PET in heart failure patients. J Nucl Cardiol. 2019.

    Article  PubMed  Google Scholar 

  15. 15.

    Slart RH, Bax JJ, van Veldhuisen DJ, van der Wall EE, Dierckx RA, de Boer J, et al. Prediction of functional recovery after revascularization in patients with coronary artery disease and left ventricular dysfunction by gated FDG-PET. J Nucl Cardiol. 2006;13:210–9.

    Article  Google Scholar 

  16. 16.

    Fuchs TA, Ghadri JR, Stehli J, Gebhard C, Kazakauskaite E, Klaeser B, et al. Hypodense regions in unenhanced CT identify nonviable myocardium: validation versus 18F-FDG PET. Eur J Nucl Med Mol Imaging. 2012;39:1920–6.

    Article  Google Scholar 

  17. 17.

    Bax JJ, Visser FC, Poldermans D, van Lingen A, Elhendy A, Boersma E, et al. Feasibility, safety and image quality of cardiac FDG studies during hyperinsulinaemic-euglycaemic clamping. Eur J Nucl Med Mol Imaging. 2002;29:452–7.

    CAS  Article  Google Scholar 

  18. 18.

    Lizunov VA, Stenkula KG, Lisinski I, Gavrilova O, Yver DR, Chadt A, et al. Insulin stimulates fusion, but not tethering, of GLUT4 vesicles in skeletal muscle of HA-GLUT4-GFP transgenic mice. Am J Physiol Endocrinol Metab. 2012;302:E950–60.

    CAS  Article  Google Scholar 

  19. 19.

    Jezewski AJ, Larson JJ, Wysocki B, Davis PH, Wysocki T. A novel method for simulating insulin mediated GLUT4 translocation. Biotechnol Bioeng. 2014;111:2454–65.

    CAS  Article  Google Scholar 

  20. 20.

    Szablewski L. Glucose transporters in healthy heart and in cardiac disease. Int J Cardiol. 2017;230:70–5.

    Article  Google Scholar 

  21. 21.

    Vitale GD, deKemp RA, Ruddy TD, Williams K, Beanlands RS. Myocardial glucose utilization and optimization of (18)F-FDG PET imaging in patients with non-insulin-dependent diabetes mellitus, coronary artery disease, and left ventricular dysfunction. J Nucl Med. 2001;42:1730–6.

    CAS  PubMed  Google Scholar 

  22. 22.

    Kobylecka M, Mazurek T, Fronczewska-Wieniawska K, Fojt A, Słowikowska A, Mączewska J, et al. Assessment of the myocardial FDG-PET image quality with the use of maximal Standardized Uptake Value myocardial to background index. Application of the results in regard to semiquantitative assessment of myocardial viability with cardiac dedicated software. Nucl Med Rev Cent East Eur. 2017;20:69-75.

  23. 23.

    Schinkel AF, Bax JJ, Valkema R, Elhendy A, van Domburg RT, Vourvouri EC, et al. Effect of diabetes mellitus on myocardial 18F-FDG SPECT using acipimox for the assessment of myocardial viability. J Nucl Med. 2003;44:877–83.

    PubMed  Google Scholar 

  24. 24.

    Cai X, Han X, Zhou X, Zhou L, Zhang S, Ji L. Associated factors with biochemical hypoglycemia during an oral glucose tolerance test in a Chinese population. J Diabetes Res. 2017;3212814.

  25. 25.

    Morio R, Hyogo H, Hatooka M, Morio K, Kan H, Kobayashi T, et al. The risk of transient postprandial oxyhypoglycemia in nonalcoholic fatty liver disease. J Gastroenterol. 2017;52:253–62.

    CAS  Article  Google Scholar 

  26. 26.

    Sherwin RS, Kramer KJ, Tobin JD, Insel PA, Liljenquist JE, Berman M, et al. A model of the kinetics of insulin in man. J Clin Invest. 1974;53:1481–92.

    CAS  Article  Google Scholar 

Download references


The trial was supported by Natural Science Foundation of Fujian Province (2015J01516, 2018J01202), Quanzhou Science and Technology Commission (2019C023R), and National Natural Science Foundation of China (81601525).

Conflict of Interest

No disclosures.

Author information



Corresponding author

Correspondence to Yang Chun Chen MD, PhD.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

(PPTX 2063 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Chen, Y.C., Wang, Q.Q., Wang, Y.H. et al. Intravenous regular insulin is an efficient and safe procedure for obtaining high-quality cardiac 18F-FDG PET images: an open-label, single-center, randomized controlled prospective trial. J. Nucl. Cardiol. (2020).

Download citation

Key Words

  • F18-Fluorodeoxyglucose
  • insulin
  • glucose
  • myocytes
  • cardiac