Comparison of 18F-FDG and 68Ga PET imaging in the assessment of experimental osteomyelitis due to Staphylococcus aureus

  • Tatu J. Mäkinen
  • Petteri Lankinen
  • Tiina Pöyhönen
  • Jari Jalava
  • Hannu T. Aro
  • Anne RoivainenEmail author
Original Article



Although positron emission tomography (PET) using 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) is a promising imaging modality for bone infections, the technique may still give false-positive results due to unspecific uptake in healing bone. This experimental study compared 18F-FDG and 68Ga in PET imaging of osteomyelitis and normal bone healing.


A diffuse osteomyelitis model of the tibia was applied in the rat (n=50). Two weeks after operation, PET imaging with 18F-FDG and 68Ga was performed, followed by peripheral quantitative computed tomography (pQCT) and radiography. Osteomyelitis was verified by quantitative bacteriology. In addition to in vivo imaging, ex vivo measurements of tissue radioactivity were performed to verify uptake of the tracers.


Compared with controls with normal bone healing, the osteomyelitic tibias showed increased SUV ratios (i.e. radioactivity ratios between the operated and non-operated sides) for both 18F-FDG (1.74±0.37) and 68Ga (1.62±0.28) (P<0.001). Ex vivo measurements also showed increased tracer accumulation in the infected bone (P=0.003 for 18F-FDG and P<0.001 for 68Ga). The intensity of 68Ga uptake reflected pathological changes of osteomyelitic bones measured by pQCT. The uptake of 18F-FDG, however, did not show as close a correlation with the anatomical changes. The healing bones without infection exhibited slightly elevated uptake of 18F-FDG (SUV ratio 1.16±0.06), but 68Ga did not accumulate in the healing bone, as judged on the basis of both in vivo imaging (SUV ratio 1.02±0.05) and ex vivo measurements (SUV 0.92±0.21) (P=0.003 and P=0.022 compared with 18F-FDG uptake, respectively).


This study suggests the feasibility of 68Ga PET imaging of bone infections. However, further studies are needed to clarify the value of 68Ga PET for clinical purposes.


Infectious disease PET Osteomyelitis 18F-FDG 68Ga 



This work was funded by grants from the National Technology Agency of Finland (TEKES), Academy of Finland (grants No. 205757 and No. 103032), the Instrumentarium Foundation and the Finnish Cultural Foundation. T.J.M. and P.L. are PhD students supported by the Finnish Graduate School for Musculoskeletal Diseases. The authors thank Anni Virolainen-Julkunen, MD, PhD, for conducting the PFGE analysis and Tero Vahlberg, MSc, for statistical consultation.


  1. 1.
    Guhlmann A, Brecht-Krauss D, Suger G, Glatting G, Kotzerke J, Kinzl L, et al. Fluorine-18-FDG PET and technetium-99m antigranulocyte antibody scintigraphy in chronic osteomyelitis. J Nucl Med 1998;39:2145–52PubMedGoogle Scholar
  2. 2.
    Kälicke T, Schmitz A, Risse JH, Arens S, Keller E, Hansis M, et al. Fluorine-18 fluorodeoxyglucose PET in infectious bone diseases: results of histologically confirmed cases. Eur J Nucl Med 2000;27:524–8PubMedCrossRefGoogle Scholar
  3. 3.
    de Winter F, van de Wiele C, Vogelaers D, de Smet K, Verdonk B, Dierckx RA. Fluorine-18 fluorodeoxyglucose-positron emission tomography: a highly accurate imaging modality for the diagnosis of chronic musculoskeletal infections. J Bone Joint Surg 2001;83A:651–60Google Scholar
  4. 4.
    Stumpe KD, Dazzi H, Schaffner A, von Schulthess GK. Infection imaging using whole-body FDG-PET. Eur J Nucl Med 2000;27:822–32PubMedCrossRefGoogle Scholar
  5. 5.
    Ichiya Y, Kuwabara Y, Sasaki M, Yoshida T, Akashi Y, Murayama S, et al. FDG-PET in infectious lesions: the detection and assessment of lesion activity. Ann Nucl Med 1996;10:185–91PubMedCrossRefGoogle Scholar
  6. 6.
    Sugawara Y, Gutowski TD, Fisher SJ, Brown RS, Wahl RL. Uptake of positron emission tomography tracers in experimental bacterial infections: a comparative biodistribution study of radiolabeled FDG, thymidine, L-methionine, 67Ga-citrate, and 125I-HSA. Eur J Nucl Med 1999;26:333–41PubMedCrossRefGoogle Scholar
  7. 7.
    Einhorn TA. The cell and molecular biology of fracture healing. Clin Orthop 1998;355S:7–21CrossRefGoogle Scholar
  8. 8.
    de Winter F, Vogelaers D, Gemmel F, Dierckx RA. Promising role of 18-F-fluoro-D-deoxyglucose positron emission tomography in clinical infectious diseases. Eur J Clin Microbiol Infect Dis 2002;21:247–57PubMedCrossRefGoogle Scholar
  9. 9.
    Koort JK, Mäkinen TJ, Knuuti J, Jalava J, Aro HT. Comparative 18F-FDG-PET imaging of experimental Staphylococcus aureus osteomyelitis and normal bone healing. J Nucl Med 2004;45:1406–11PubMedGoogle Scholar
  10. 10.
    Palestro CJ. The current role of gallium imaging in infection. Semin Nucl Med 1994;24:128–41PubMedCrossRefGoogle Scholar
  11. 11.
    Chianelli M, Mather SJ, Martin-Comin J, Signore A. Radiopharmaceuticals for the study of inflammatory processes: a review. Nucl Med Commun 1997;18:437–55PubMedCrossRefGoogle Scholar
  12. 12.
    Peters AM. The utility of 99mTc HMPAO-leukocytes for imaging infection. Semin Nucl Med 1994;24:110–27PubMedCrossRefGoogle Scholar
  13. 13.
    Datz FL. Abdominal abscess detection: gallium, 111In-, and 99mTc-labeled leukocytes, and polyclonal and monoclonal antibodies. Semin Nucl Med 1996;26:51–64PubMedCrossRefGoogle Scholar
  14. 14.
    Alazraki NP. Gallium-67 imaging in infection. In: Early PJ, Sodee DB, editors. Principles and practice of nuclear medicine, 2nd ed. St. Louis: Mosby-Year Book; 1995. p. 702–13Google Scholar
  15. 15.
    Roivainen A, Tolvanen T, Salomäki S, Lendvai G, Velikyan I, Numminen P, et al. 68Ga-labeled oligonucleotides for in vivo imaging with PET. J Nucl Med 2004;45:347–55PubMedGoogle Scholar
  16. 16.
    Rissing JP. Animal models of osteomyelitis. Knowledge, hypothesis, and speculation. Infect Dis Clin North Am 1990;4:377–90PubMedGoogle Scholar
  17. 17.
    Mader JT. Animal models of osteomyelitis. Am J Med 1985;78:213–7PubMedCrossRefGoogle Scholar
  18. 18.
    O’Reilly T, Mader JT. Rat model of bacterial osteomyelitis of the tibia. In: Zak O, Sande MA, editors. Handbook of animal models of infection. Bath, Avon, UK: Academic; 1999. p. 561–75CrossRefGoogle Scholar
  19. 19.
    Nelson DR, Buxton TB, Luu QN, Rissing JP. The promotional effect of bone wax on experimental Staphylococcus aureus osteomyelitis. J Thorac Cardiovasc Surg 1990;99:977–80PubMedGoogle Scholar
  20. 20.
    Hamacher K, Coenen HH, Stocklin G. Efficient stereospecific synthesis of no-carrier-added 2-[18F]-fluoro-2-deoxy-D-glucose using aminopolyether supported nucleophilic substitution. J Nucl Med 1986;27:235–8PubMedGoogle Scholar
  21. 21.
    DeGrado TR, Turkington TG, Williams JJ, Stearns CW, Hoffman JM, Coleman RE. Performance characteristics of a whole-body PET scanner. J Nucl Med 1994;35:1398–1406PubMedGoogle Scholar
  22. 22.
    Rissing JP, Buxton TB, Weinstein RS, Shockley RK. Model of experimental chronic osteomyelitis in rats. Infect Immun 1985;47:581–6PubMedCentralPubMedGoogle Scholar
  23. 23.
    van Griethuysen A, Bes M, Etienne J, Zbinden R, Kluytmans J. International multicenter evaluation of latex agglutination tests for identification of Staphylococcus aureus. J Clin Microbiol 2001;39:86–9PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Petty W, Spanier S, Shuster JJ, Silverthorne C. The influence of skeletal implants on incidence of infection. Experiments in a canine model. J Bone Joint Surg 1985;67A:1236–44Google Scholar
  25. 25.
    Hnatowich DJ. A review of radiopharmaceutical development with short-lived generator-produced radionuclides other than 99mTc. Int J Appl Radiat Isot 1977;28:169–81PubMedCrossRefGoogle Scholar
  26. 26.
    Oyen WJ, Boerman OC, van der Laken CJ, Claessens RA, van der Meer JW, Corstens FH. The uptake mechanisms of inflammation- and infection-localizing agents. Eur J Nucl Med 1996;23:459–65PubMedCrossRefGoogle Scholar
  27. 27.
    Green MA, Welch MJ. Gallium radiopharmaceutical chemistry. Int J Rad Appl Instrum B 1989;16:435–48PubMedCrossRefGoogle Scholar
  28. 28.
    Hoffman EJ, Huang SC, Phelps ME. Quantitation in positron emission computed tomography: 1. Effect of object size. J Comput Assist Tomogr 1979;3:299–308PubMedCrossRefGoogle Scholar
  29. 29.
    Boellaard R, Krak NC, Hoekstra OS, Lammertsma AA. Effects of noise, image resolution, and ROI definition on the accuracy of standard uptake values: a simulation study. J Nucl Med 2004;45:1519–27PubMedGoogle Scholar
  30. 30.
    Visvikis D, Cheze-LeRest C, Costa DC, Bomanji J, Gacinovic S, Ell PJ. Influence of OSEM and segmented attenuation correction in the calculation of standardised uptake values for [18F]FDG PET. Eur J Nucl Med 2001;28:1326–35PubMedCrossRefGoogle Scholar
  31. 31.
    Boellaard R, van Lingen A, Lammertsma AA. Experimental and clinical evaluation of iterative reconstruction (OSEM) in dynamic PET: quantitative characteristics and effects on kinetic modeling. J Nucl Med 2001;42:808–17PubMedGoogle Scholar
  32. 32.
    Gratz S, Béhé M, Boerman OC, Kunze E, Schulz H, Eiffert H, et al. 99mTc-E-selectin binding peptide for imaging acute osteomyelitis in a novel rat model. Nucl Med Commun 2001;22:1003–13PubMedCrossRefGoogle Scholar
  33. 33.
    Sammak B, Abd El Bagi M, Al Shahed M, Hamilton D, Al Nabulsi J, Youssef B, et al. Osteomyelitis: a review of currently used imaging techniques. Eur Radiol 1999;9:894–900PubMedCrossRefGoogle Scholar
  34. 34.
    Govender S, Csimma C, Genant HK, Valentin-Opran A, Amit Y, Arbel R, et al. Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients. J Bone Joint Surg 2002;84A:2123–34Google Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Tatu J. Mäkinen
    • 1
  • Petteri Lankinen
    • 1
  • Tiina Pöyhönen
    • 2
  • Jari Jalava
    • 3
  • Hannu T. Aro
    • 1
  • Anne Roivainen
    • 2
    Email author
  1. 1.Orthopaedic Research Unit, Department of Orthopaedic Surgery and TraumatologyUniversity of TurkuTurkuFinland
  2. 2.Turku PET CentreTurku University HospitalTurkuFinland
  3. 3.Department of Human Microbial Ecology and InflammationNational Public Health InstituteTurkuFinland

Personalised recommendations