Log in

Effects of Fever on 18F-FDG Distribution In Vivo: a Preliminary Study

  • Research Article
  • Published:
Molecular Imaging and Biology Aims and scope Submit manuscript

Abstract

Purpose

Elevated body temperature might change glucose metabolism in human organs. The purpose of this study is to explore 18F-FDG distribution in febrile patients on the day of 18F-FDG PET/CT scanning and compare it with patients with a normal temperature.

Procedures

18F-FDG PET/CT was performed on 69 febrile patients and 82 patients with a normal temperature. Patient sociodemographic data, blood glucose levels before PET/CT, body temperature on the day of the exam, and laboratory test results were collected. Maximal standard uptake values (SUVmax) in the brain, mediastinal blood pool, liver, spleen, and the bone marrow were compared.

Results

Compared with the controls, SUVmax of the febrile patients was significantly lower in the brain, mediastinal blood pool, and the liver (p < 0.01), and higher in the spleen and bone marrow (p < 0.01). In the febrile group, SUVmax was not significantly different between the FDG burden and non-FDG burden patients (p > 0.05). Body temperature was found negatively correlated with SUVmax in the brain (r = − 0.646), mediastinal blood pool (r = − 0.530), and the liver (r = − 0.384), and positively correlated with the SUVmax in the spleen (r = 0.592) and bone marrow (r = 0.651). Multivariate linear regression established body temperature on the day of PET/CT as an independent affecting factor (p < 0.01) for the SUVmax in the brain, mediastinal blood pool, liver, spleen, and bone marrow. The SUV in the brain, liver, and mediastinal blood pool remained different (p < 0.05) after corrected with the SUVmax in the blood pool or liver.

Conclusions

Fever influences 18F-FDG distribution in multiple human tissues and organs. Altered 18F-FDG distribution in vivo might affect results of disease lesion detection and tumor therapy response assessment. Correction with blood pool or liver SUV fails to cancel the effects of fever. The day of fever should be avoided for PET/CT scan, especially in assessing tumor therapy response.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.

Similar content being viewed by others

References

  1. von Schulthess GK, Steinert HC, Hany TF (2006) Integrated PET/CT: current applications and future directions. Radiology 238(2):405–422

    Google Scholar 

  2. Blodgett TM, Meltzer CC, Townsend DW (2007) PET/CT: form and function. Radiology 242(2):360–385

    PubMed  Google Scholar 

  3. Smith-Bindman R, Miglioretti DL, Johnson E, Lee C, Feigelson HS, Flynn M, Greenlee RT, Kruger RL, Hornbrook MC, Roblin D, Solberg LI, Vanneman N, Weinmann S, Williams AE (2012) Use of diagnostic imaging studies and associated radiation exposure for patients enrolled in large integrated health care systems, 1996-2010. JAMA 307(22):2400–2409

    CAS  PubMed  Google Scholar 

  4. Hashefi M, Curiel R (2011) Future and upcoming non-neoplastic applications of PET/CT imaging. Ann N Y Acad Sci 1228:167–174

    CAS  PubMed  Google Scholar 

  5. Wahl RL, Jacene H, Kasamon Y, Lodge MA (2009) From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med 50(Suppl 1):122S–150S

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Higgins KA, Hoang JK, Roach MC, Chino J, Yoo DS, Turkington TG, Brizel DM (2012) Analysis of pretreatment FDG-PET SUV parameters in head-and-neck cancer: tumor SUVmean has superior prognostic value. Int J Radiat Oncol Biol Phys 82(2):548–553

  7. Na F, Wang J, Li C, Deng L, Xue J, Lu Y (2014) Primary tumor standardized uptake value measured on F18-fluorodeoxyglucose positron emission tomography is of prediction value for survival and local control in non-small-cell lung cancer receiving radiotherapy: meta-analysis. J Thorac Oncol 9(6):834–842

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Boktor RR, Walker G, Stacey R, Gledhill S, Pitman AG (2013) Reference range for intrapatient variability in blood-pool and liver SUV for 18F-FDG PET. J Nucl Med 54(5):677–682

    CAS  PubMed  Google Scholar 

  9. Thie JA (2014) Understanding SUV variability in reference tissue for 18F-FDG PET with a simple measurement model. J Nucl Med 55(2):352

    CAS  PubMed  Google Scholar 

  10. Viglianti BL, Wong KK, Wimer SM, Parameswaran A, Nan B, Ky C, Townsend DM, Rubello D, Frey KA, Gross MD (2017) Effect of hyperglycemia on brain and liver (18)F-FDG standardized uptake value (FDG SUV) measured by quantitative positron emission tomography (PET) imaging. Biomed Pharmacother 88:1038–1045

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Viglianti BL, Wale DJ, Wong KK, Johnson TD, Ky C, Frey KA, Gross MD (2018) Effects of tumor burden on reference tissue standardized uptake for PET imaging: modification of PERCIST criteria. Radiology:171356

  12. Dong MJ, Lin XT, Zhao J, Guan YH, Zuo CT, Chen X, Dai JZ, Jiang BD (2006) Malignant tumor with false negative 18F-FDG PET image. Zhonghua zhong liu za zhi [Chin J Oncol] 28(9):713–717

    Google Scholar 

  13. Roarke MC, Nguyen BD, Pockaj BA (2008) Desmoplastic melanoma: true positive and false negative findings on F-18 FDG-PET/CT. Clin Nucl Med 33(8):562–564

    PubMed  Google Scholar 

  14. Mahmood S, Martinez de Llano SR (2008) Paget disease of the humerus mimicking metastatic disease in a patient with metastatic malignant mesothelioma on whole body F-18 FDG PET/CT. Clin Nucl Med 33(7):510–512

    PubMed  Google Scholar 

  15. Acar C, Akkas BE, Sen I, Sozen S, Kitapci MT (2008) False positive 18F-FDG PET scan in adrenal oncocytoma. Urol Int 80(4):444–447

    CAS  PubMed  Google Scholar 

  16. Kim IJ, Kim SJ, Kim YK (2009) Age- and sex-associated changes in cerebral glucose metabolism in normal healthy subjects: statistical parametric map** analysis of F-18 fluorodeoxyglucose brain positron emission tomography. Acta Radiol 50(10):1169–1174

    PubMed  Google Scholar 

  17. Zhu H, Goris M (2012) Factors affecting brain metabolism measured with 18FDG. Open J Med Imaging 2(1):19–22

    Google Scholar 

  18. Hsieh TC, Lin WY, Ding HJ, Sun SS, Wu YC, Yen KY, Kao CH (2012) Sex- and age-related differences in brain FDG metabolism of healthy adults: an SPM analysis. J Neuroimaging Off J Am Soc Neuroimaging 22(1):21–27

  19. Busing KA, Schonberg SO, Brade J, Wasser K (2013) Impact of blood glucose, diabetes, insulin, and obesity on standardized uptake values in tumors and healthy organs on 18F-FDG PET/CT. Nucl Med Biol 40(2):206–213

    PubMed  Google Scholar 

  20. Blatteis CM (2003) Fever: pathological or physiological, injurious or beneficial? J Therm Biol 28(1):1–13

    Google Scholar 

  21. Cannon JG (2013) Perspective on fever: the basic science and conventional medicine. Complement Ther Med 21(Suppl 1):S54–S60

    PubMed  Google Scholar 

  22. Shivamurthy VK, Tahari AK, Marcus C, Subramaniam RM (2015) Brain FDG PET and the diagnosis of dementia. AJR Am J Roentgenol 204(1):W76–W85

    PubMed  Google Scholar 

  23. Chiba Y, Iseki E, Fujishiro H, Ota K, Kasanuki K, Suzuki M, Hirayasu Y, Arai H, Sato K (2016) Early differential diagnosis between Alzheimer’s disease and dementia with Lewy bodies: comparison between (18)F-FDG PET and (123)I-IMP SPECT. Psychiatry Res 249:105–112

  24. Juweid ME, Stroobants S, Hoekstra OS, Mottaghy FM, Dietlein M, Guermazi A, Wiseman GA, Kostakoglu L, Scheidhauer K, Buck A, Naumann R, Spaepen K, Hicks RJ, Weber WA, Reske SN, Schwaiger M, Schwartz LH, Zijlstra JM, Siegel BA, Cheson BD (2007) Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol Off J Am Soc Clin Oncol 25(5):571–578

  25. Cheson BD (2018) PET/CT in lymphoma: current overview and future directions. Semin Nucl Med 48(1):76–81

    PubMed  Google Scholar 

  26. Karls S, Shah H, Jacene H (2018) PET/CT for lymphoma post-therapy response assessment in other lymphomas, response assessment for autologous stem cell transplant, and lymphoma follow-up. Semin Nucl Med 48(1):37–49

    PubMed  Google Scholar 

  27. Kobe C, Dietlein M, Hellwig D (2018) PET/CT for lymphoma post-therapy response assessment in Hodgkin lymphoma and diffuse large B-cell lymphoma. Semin Nucl Med 48(1):28–36

    PubMed  Google Scholar 

  28. Fallanca F, Alongi P, Incerti E, Gianolli L, Picchio M, Bomanji J (2015) Deauville criteria and international harmonization project criteria at the end of 1st line therapy in lymphoma patients: response assessment and prognostic evaluation. J Nucl Med 56(3):1355–1355

  29. Fueger BJ, Czernin J, Hildebrandt I, Tran C, Halpern BS, Stout D, Phelps ME, Weber WA (2006) Impact of animal handling on the results of 18F-FDG PET studies in mice. J Nucl Med 47(6):999–1006

    CAS  PubMed  Google Scholar 

  30. Wan XH, Lu XF (2013) Diagnostics. In: Common symptoms, 8th edn. People’s Medical Publishing House, Bei**g, pp 8–9

    Google Scholar 

  31. Meller J, Altenvoerde G, Munzel U, Jauho A, Behe M, Gratz S, Luig H, Becker W (2000) Fever of unknown origin: prospective comparison of [18F]FDG imaging with a double-head coincidence camera and gallium-67 citrate SPET. Eur J Nucl Med 27(11):1617–1625

    CAS  PubMed  Google Scholar 

  32. Bleeker-Rovers CP, de Kleijn EM, Corstens FH, van der Meer JW, Oyen WJ (2004) Clinical value of FDG PET in patients with fever of unknown origin and patients suspected of focal infection or inflammation. Eur J Nucl Med Mol Imaging 31(1):29–37

    PubMed  Google Scholar 

  33. Besson FL, Chaumet-Riffaud P, Playe M, Noel N, Lambotte O, Goujard C, Prigent A, Durand E (2016) Contribution of (18)F-FDG PET in the diagnostic assessment of fever of unknown origin (FUO): a stratification-based meta-analysis. Eur J Nucl Med Mol Imaging 43(10):1887–1895

    CAS  PubMed  Google Scholar 

  34. Mrozek S, Vardon F, Geeraerts T (2012) Brain temperature: physiology and pathophysiology after brain injury. Anesthesiol Res Pract 2012:989487

    PubMed  PubMed Central  Google Scholar 

  35. Baracos VE, Whitmore WT, Gale R (1987) The metabolic cost of fever. Can J Physiol Pharmacol 65(6):1248–1254

    CAS  PubMed  Google Scholar 

  36. Stocchetti N, Protti A, Lattuada M, Magnoni S, Longhi L, Ghisoni L, Egidi M, Zanier ER (2005) Impact of pyrexia on neurochemistry and cerebral oxygenation after acute brain injury. J Neurol Neurosurg Psychiatry 76(8):1135–1139

  37. Szablewski L (2013) Expression of glucose transporters in cancers. Biochim Biophys Acta 1835(2):164–169

    CAS  PubMed  Google Scholar 

  38. Kostakoglu L, Hardoff R, Mirtcheva R, Goldsmith SJ (2004) PET-CT fusion imaging in differentiating physiologic from pathologic FDG uptake. Radiographics 24(5):1411–1431

    PubMed  Google Scholar 

  39. Zucker S, Friedman S, Lysik RM (1974) Bone marrow erythropoiesis in the anemia of infection, inflammation, and malignancy. J Clin Invest 53(4):1132–1138

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Adams HJ, Kwee TC, Fijnheer R, Dubois SV, Nievelstein RA, de Klerk JM (2015) Diffusely increased bone marrow FDG uptake in recently untreated lymphoma: incidence and relevance. Eur J Haematol 95(1):83–89

    CAS  PubMed  Google Scholar 

  41. Hapkido H, Kartamihardja AS (2016) Differential diagnosis of diffuse bone marrow uptake on 18F-FDG PET/CT. Int J Clin Biomed Res 2(1):1–5

    Google Scholar 

  42. Berthet L, Cochet A, Kanoun S, Berriolo-Riedinger A, Humbert O, Toubeau M, Dygai-Cochet I, Legouge C, Casasnovas O, Brunotte F (2013) In newly diagnosed diffuse large B-cell lymphoma, determination of bone marrow involvement with 18F-FDG PET/CT provides better diagnostic performance and prognostic stratification than does biopsy. J Nucl Med 54(8):1244–1250

  43. Li J, Huang Y, Ji T, Tan R, Chen W (2002) Study on multi-parameter dynamic measurement of the elastic properties of red blood cell membrane based on image analyzing technique. Acta Biophys Sin 18(3):350–354

    Google Scholar 

  44. Mebius RE, Kraal G (2005) Structure and function of the spleen. Nat Rev Immunol 5(8):606–616

    CAS  Google Scholar 

  45. Pivkin IV, Peng Z, Karniadakis GE, Buffet PA, Dao M, Suresh S (2016) Biomechanics of red blood cells in human spleen and consequences for physiology and disease. Proc Natl Acad Sci U S A 113(28):7804–7809

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Ohnhaus EE, Tilvis R (1976) Liver blood flow. Metabolic heat production and body temperature before, during and after phenobarbitone administration. Acta Hepatogastroenterol 23(6):404–408

    CAS  Google Scholar 

  47. Kisauzi DN, Leek BF (1991) The effects of experimentally induced fever on the estimated blood flow to and oxygen utilization by the liver and the viscera drained by the portal vein in sheep. Vet Res Commun 15(2):95–105

    CAS  PubMed  Google Scholar 

  48. Walter EJ, Hanna-Jumma S, Carraretto M, Forni L (2016) The pathophysiological basis and consequences of fever. Crit Care 20(1):200

    PubMed  PubMed Central  Google Scholar 

  49. Malladi A, Viner M, Jackson T, Mercier G, Subramaniam RM (2013) PET/CT mediastinal and liver FDG uptake: effects of biological and procedural factors. J Med Imaging Radiat Oncol 57(2):169–175

    PubMed  Google Scholar 

  50. Lin CY, Ding HJ, Lin T, Lin CC, Kuo TH, Kao CH (2010) Positive correlation between serum liver enzyme levels and standard uptake values of liver on FDG-PET. Clin Imaging 34(2):109–112

    PubMed  Google Scholar 

  51. Liu G, Li Y, Hu P, Cheng D, Shi H (2015) The combined effects of serum lipids, BMI, and fatty liver on 18F-FDG uptake in the liver in a large population from China: an 18F-FDG-PET/CT study. Nucl Med Commun 36(7):709–716

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Yutang Yao, Junjun Cheng, Minggang Su, and **aohong Ou. The first draft of the manuscript was written by Yutang Yao and Junjun Cheng. The draft was reviewed and edited by Minggang Su and **aohong Ou. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Minggang Su or **aohong Ou.

Ethics declarations

Ethical Approval

For this type of study, formal consent is not required.

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yao, Y., Cheng, J., Su, M. et al. Effects of Fever on 18F-FDG Distribution In Vivo: a Preliminary Study. Mol Imaging Biol 22, 1116–1123 (2020). https://doi.org/10.1007/s11307-020-01486-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11307-020-01486-9

Key words

Navigation