Factors influencing the pattern and intensity of myocardial 18F-FDG uptake in oncologic PET-CT imaging

Document Type : Original Article

Authors

Research Center for Nuclear Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Introduction:Myocardial 18F-FDG uptake is highly variable in oncologic whole body 18F-FDG PET/CT studies, ranging from quite intense to minimal distribution. Intense or heterogeneous myocardial 18F-FDG uptake is undesirable as it may interfere with the visual or quantitative evaluation of tumoral invasion and metastases in pericardium, myocardium or adjacent mediastinal structures. The diet, as well as many other factors, is assumed to influence the myocardial 18F-FDG uptake. Using a multivariate model, we tried to identify and predict the main factors influencing cardiac 18F-FDG uptake in patients referred for oncologic PET/CT evaluation.
Methods: A total of 214 patients referred for oncologic 18F-FDG PET/CT scan were enrolled in our study. Patients were randomly allocated into two groups according to the diet they were instructed to follow during 24-hour period before imaging.  One hundred and seven cases with a routine diet (RD) and the same number of patients with a low carbohydrate, high fat (LCHF) diet were included. All patients were fast 6 hours before imaging. Weight, height, blood glucose, heart rate, systolic and diastolic blood pressure were measured before radiotracer injection. Visual and quantitative analysis were done after imaging and the pattern of 18F-FDG uptake, as well as standardized quantitative value of cardiac uptake was determined for each case.
Results: The frequency of undesirable cardiac 18F-FDG uptake in the LCHF group was significantly less than RD group (17% vs. 72%, p<0.001). The univariate analyses showed male gender, BMI>=30 as well as consumption of cardiotoxic chemotherapeutic agents, benzodiazepines and β blockers were significantly associated with higher intensity of myocardial 18F-FDG uptake, while this undesirable finding was less evident in cases with diabetes mellitus. A multivariate logistic regression model including all of the mentioned variables revealed the diet was the only significant independent factor that predicted undesirable myocardial 18F-FDG uptake (p<0.001).

Conclusion: LCHF diet 24 hours before PET/CT imaging is the only controllable independent factor influencing the intensity and pattern of myocardial 18F-FDG uptake and is recommended as an optimal preparation to suppress cardiac 18F-FDG uptake.

Keywords

Main Subjects


  1. Boellaard R, Delgado-Bolton R, Oyen WJ, Giammarile F, Tatsch K, Eschner W, Verzijlbergen FJ, Barrington SF, Pike LC, Weber WA, Stroobants S, Delbeke D, Donohoe KJ, Holbrook S, Graham MM, Testanera G, Hoekstra OS, Zijlstra J, Visser E, Hoekstra CJ, Pruim J, Willemsen A, Arends B, Kotzerke J, Bockisch A, Beyer T, Chiti A, Krause BJ; European Association of Nuclear Medicine (EANM). FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging. 2015 Feb;42(2):328-54.
  2. Abouzied MM, Crawford ES, Nabi HA. 18F-FDG imaging: pitfalls and artifacts. J Nucl Med Technol. 2005 Sep;33(3):145-55; quiz 162-3.
  3. Fukuchi K, Ohta H, Matsumura K, Ishida Y. Benign variations and incidental abnormalities of myocardial FDG uptake in the fasting state as encountered during routine oncology positron emission tomography studies. Br J Radiol. 2007 Jan;80(949):3-11.
  4. Maurer AH, Burshteyn M, Adler LP, Steiner RM. How to differentiate benign versus malignant cardiac and paracardiac 18F FDG uptake at oncologic PET/CT. Radiographics. 2011 Sep-Oct;31(5):1287-305.
  5. Kaneta T, Hakamatsuka T, Takanami K, Yamada T, Takase K, Sato A, Higano S, Kinomura S, Fukuda H, Takahashi S, Yamada S. Evaluation of the relationship between physiological FDG uptake in the heart and age, blood glucose level, fasting period, and hospitalization. Ann Nucl Med. 2006 Apr;20(3):203-8.
  6. Williams G, Kolodny GM. Suppression of myocardial 18F-FDG uptake by preparing patients with a high-fat, low-carbohydrate diet. AJR Am J Roentgenol. 2008 Feb;190(2):W151-6.
  7. Balink H, Hut E, Pol T, Flokstra FJ, Roef M. Suppression of 18F-FDG Myocardial Uptake Using a Fat-Allowed, Carbohydrate-Restricted Diet. J Nucl Med Technol. 2011 Sep;39(3):185-9.
  8. Wykrzykowska J, Lehman S, Williams G, Parker JA, Palmer MR, Varkey S, Kolodny G, Laham R. Imaging of inflamed and vulnerable plaque in coronary arteries with 18F-FDG PET/CT in patients with suppression of myocardial uptake using a low-carbohydrate, high-fat preparation. J Nucl Med. 2009 Apr;50(4):563-8.
  9. Williams G, Kolodny GM. Suppression of myocardial 18F-FDG uptake by preparing patients with a high-fat, low-carbohydrate diet. AJR Am J Roentgenol. 2008 Feb;190(2):W151-6.
  10. Israel O, Weiler-Sagie M, Rispler S, Bar-Shalom R, Frenkel A, Keidar Z, Bar-Shalev A, Strauss HW. PET/CT quantitation of the effect of patient-related factors on cardiac 18F-FDG uptake. J Nucl Med. 2007 Feb;48(2):234-9.
  11. Wismann J, Willoughby D. Gender differences in carbohydrate metabolism and carbohydrate loading. J Int Soc Sports Nutr. 2006;3:28-34.
  12. Doenst T, Pytel G, Schrepper A, Amorim P, Färber G, Shingu Y, Mohr FW, Schwarzer M. Decreased rates of substrate oxidation ex vivo predict the onset of heart failure and contractile dysfunction in rats with pressure overload. Cardiovasc Res. 2010 Jun 1;86(3):461-70.
  13. Kolwicz SC Jr, Tian R. Glucose metabolism and cardiac hypertrophy. Cardiovasc Res. 2011 May 1;90(2):194-201.
  14. Tarnopolsky M. Gender differences in metabolism: Practical and nutritional implications. Boca Raton: CRC Press; 1999. p. 340.
  15. Chaudhary KR, El-Sikhry H, Seubert JM. Mitochondria and the aging heart. J Geriatr Cardiol. 2011 Sep;8(3):159-67.
  16. Tocchi A, Quarles EK, Basisty N, Gitari L, Rabinovitch PS. Mitochondrial dysfunction in cardiac aging. Biochim Biophys Acta. 2015 Nov;1847(11):1424-33.
  17. Henkin RE. Nuclear medicine. 2nd ed. Philadelphia: Mosby Elsevier; 2006.
  18. Aasum E, Hafstad AD, Severson DL, Larsen TS. Age-dependent changes in metabolism, contractile function, and ischemic sensitivity in hearts from db/db mice. Diabetes. 2003 Feb;52(2):434-41.
  19. Peterson LR, Herrero P, Schechtman KB, Racette SB, Waggoner AD, Kisrieva-Ware Z, Dence C, Klein S, Marsala J, Meyer T, Gropler RJ. Effect of obesity and insulin resistance on myocardial substrate metabolism and efficiency in young women. Circulation. 2004 May 11;109(18):2191-6.
  20. Zhou YT, Grayburn P, Karim A, Shimabukuro M, Higa M, Baetens D, Orci L, Unger RH. Lipotoxic heart disease in obese rats: implications for human obesity. Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1784-9.
  21. Abel ED, Litwin SE, Sweeney G. Cardiac remodeling in obesity. Physiol Rev. 2008 Apr;88(2):389-419.
  22. Park SY, Cho YR, Kim HJ, Higashimori T, Danton C, Lee MK, Dey A, Rothermel B, Kim YB, Kalinowski A, Russell KS, Kim JK. Unraveling the temporal pattern of diet-induced insulin resistance in individual organs and cardiac dysfunction in C57BL/6 mice. Diabetes. 2005 Dec;54(12):3530-40.
  23. Coort SL, Hasselbaink DM, Koonen DP, Willems J, Coumans WA, Chabowski A, van der Vusse GJ, Bonen A, Glatz JF, Luiken JJ. Enhanced sarcolemmal FAT/CD36 content and triacylglycerol storage in cardiac myocytes from obese zucker rats. Diabetes. 2004 Jul;53(7):1655-63.
  24. Ozguven MA, Karacalioglu AO, Ince S, Emer MO. Altered biodistribution of FDG in patients with type-2 diabetes mellitus. Ann Nucl Med. 2014 Jul;28(6):505-11.
  25. Herrero P, Peterson LR, McGill JB, Matthew S, Lesniak D, Dence C, Gropler RJ. Increased myocardial fatty acid metabolism in patients with type 1 diabetes mellitus. J Am Coll Cardiol. 2006 Feb 7;47(3):598-604.
  26. Peterson LR, Herrero P, McGill J, Schechtman KB, Kisrieva-Ware Z, Lesniak D, Gropler RJ. Fatty acids and insulin modulate myocardial substrate metabolism in humans with type 1 diabetes. Diabetes. 2008 Jan;57(1):32-40.
  27. Borde C, Kand P, Basu S. Enhanced myocardial fluorodeoxyglucose uptake following Adriamycin-based therapy: Evidence of early chemotherapeutic cardiotoxicity? World J Radiol. 2012 May 28;4(5):220-3.
  28. van der Pal HJ, van Dalen EC, Hauptmann M, Kok WE, Caron HN, van den Bos C, Oldenburger F, Koning CC, van Leeuwen FE, Kremer LC. Cardiac function in 5-year survivors of childhood cancer: a long-term follow-up study. Arch Intern Med. 2010 Jul 26;170(14):1247-55.
  29. de Swart J, Snoek-Klaver I, Valkema R, Kam BLR, Krenning EP. The influence of caffeine on the uptake of 18-FDG in the myocardium. Eur J Nucl Med Mol Imaging. 2004;31(suppl):S484.
  30. Lam MGE, Dekkers EJM, van Dongen AJ, van Isselt JW, van Rijk PP. Does caffeine influence myocardial FDG uptake? Eur J Nucl Med Mol I. 2004;31(suppl):S205.
  31. Maurer AH, Burshteyn M, Adler LP, Steiner RM. How to differentiate benign versus malignant cardiac and paracardiac 18F FDG uptake at oncologic PET/CT. Radiographics. 2011 Sep-Oct;31(5):1287-305.
  32. Tahara N, Tahara A, Nitta Y, Kodama N, Mizoguchi M, Kaida H, Baba K, Ishibashi M, Hayabuchi N, Narula J, Imaizumi T. Heterogeneous myocardial FDG uptake and the disease activity in cardiac sarcoidosis. JACC Cardiovasc Imaging. 2010 Dec;3(12):1219-28.
  33. Unal K, Unlu M, Akdemir O, Akmansu M. 18F-FDG PET/CT findings of radiotherapy-related myocardial changes in patients with thoracic malignancies. Nucl Med Commun. 2013 Sep;34(9):855-9.
  34. Abel ED, O'Shea KM, Ramasamy R. Insulin resistance: metabolic mechanisms and consequences in the heart. Arterioscler Thromb Vasc Biol. 2012 Sep;32(9):2068-76.
  35. Dirkx E, Schwenk RW, Glatz JF, Luiken JJ, van Eys GJ. High fat diet induced diabetic cardiomyopathy. Prostaglandins Leukot Essent Fatty Acids. 2011 Nov;85(5):219-25.
  36.  Zhang L, Ussher JR, Oka T, Cadete VJ, Wagg C, Lopaschuk GD. Cardiac diacylglycerol accumulation in high fat-fed mice is associated with impaired insulin-stimulated glucose oxidation. Cardiovasc Res. 2011 Jan 1;89(1):148-56.
  37. Unger RH, Orci L. Lipoapoptosis: its mechanism and its diseases. Biochim Biophys Acta. 2002 Dec 30;1585(2-3):202-12.
  38. Fine EJ, Miao W, Koba W, Volek JS, Blaufox MD. Chronic effects of dietary carbohydrate variation on [18F]-2-fluoro-2-deoxyglucose uptake in rodent heart. Nucl Med Commun. 2009 Sep;30(9):675-80.
  39. Frayn KN. The glucose-fatty acid cycle: a physiological perspective. Biochem Soc Trans. 2003 Dec;31(Pt 6):1115-9.
  40. Armoni M, Harel C, Bar-Yoseph F, Milo S, Karnieli E.Free fatty acids repress the GLUT4 gene expression in cardiac muscle via novel response elements. J Biol Chem. 2005 Oct 14;280(41):34786-95.
  41. Domenighetti AA, Danes VR, Curl CL, Favaloro JM, Proietto J, Delbridge LM. Targeted GLUT-4 deficiency in the heart induces cardiomyocyte hypertrophy and impaired contractility linked with Ca(2+) and proton flux dysregulation. J Mol Cell Cardiol. 2010 Apr;48(4):663-72.
  42. Cussó L, Vaquero JJ, Bacharach S, Desco M. Comparison of methods to reduce myocardial 18F-FDG uptake in mice: calcium channel blockers versus high-fat diets. PLoS One. 2014 Sep 19;9(9):e107999.
  43. Tsuchiya K, Tanaka J, Shuiqing Y, Welch CL, DePinho RA, Tabas I, Tall AR, Goldberg IJ, Accili D. FoxOs integrate pleiotropic actions of insulin in vascular endothelium to protect mice from atherosclerosis. Cell Metab. 2012 Mar 7;15(3):372-81.