Prosthetic joint infections: radionuclide state-of-the-art imaging

  • Filip Gemmel
  • Hans Van den Wyngaert
  • Charito Love
  • M. M. Welling
  • Paul Gemmel
  • Christopher J. Palestro
Review Article

Abstract

Prosthetic joint replacement surgery is performed with increasing frequency. Overall the incidence of prosthetic joint infection (PJI) and subsequently prosthesis revision failure is estimated to be between 1 and 3%. Differentiating infection from aseptic mechanical loosening, which is the most common cause of prosthetic failure, is especially important because of different types of therapeutic management. Despite a thorough patient history, physical examination, multiple diagnostic tests and complex algorithms, differentiating PJI from aseptic loosening remains challenging. Among imaging modalities, radiographs are neither sensitive nor specific and cross-sectional imaging techniques, such as computed tomography and magnetic resonance imaging, are limited by hardware-induced artefacts. Radionuclide imaging reflects functional rather than anatomical changes and is not hampered by the presence of a metallic joint prosthesis. As a result scintigraphy is currently the modality of choice in the investigation of suspected PJI. Unfortunately, there is no true consensus about the gold standard technique since there are several drawbacks and limitations inherent to each modality. Bone scintigraphy (BS) is sensitive for identifying the failed joint replacement, but cannot differentiate between infection and aseptic loosening. Combined bone/gallium scintigraphy (BS/GS) offers modest improvement over BS alone for diagnosing PJI. However, due to a number of drawbacks, BS/GS has generally been superseded by other techniques but it still may have a role in neutropenic patients. Radiolabelled leucocyte scintigraphy remains the gold standard technique for diagnosing neutrophil-mediated processes. It seems to be that combined in vitro labelled leucocyte/bone marrow scintigraphy (LS/BMS), with an accuracy of about 90%, is currently the imaging modality of choice for diagnosing PJI. There are, however, significant limitations using in vitro labelled leucocytes and considerable effort has been devoted to developing alternative radiotracers, such as radiolabelled HIGs, liposomes, antigranulocyte antibodies and fragments, as well as more investigational tracers such as radiolabelled antibiotics, antimicrobial peptides, bacteriophages and thymidine kinase. On the other hand, positron emission tomography (PET) is still growing in the field of PJI imaging with radiotracers such as 18F-fluorodeoxyglucose (FDG), 18F-FDG white blood cells and 18F-fluoride. But unfortunately this superb tomographic technique will only receive full acceptance when specific PET uptake patterns can be successfully developed. The emergence of hybrid modality imaging using integrated single photon emission computed tomography (SPECT) and PET with computed tomography (SPECT/CT and PET/CT) may also have a contributing role for more accurate assessment of joint replacement complications, especially combined with new radiotracers such as 68Ga and 64Cu. Finally, in searching for infection-specific tracers, currently there is no such diagnostic agent available.

Keywords

Prosthetic joint infection Preoperative diagnosis Radionuclide imaging Hybrid imaging 

References

  1. 1.
    Anguita-Alonso P, Hanssen AD, Patel R. Prosthetic joint infection. Expert Rev Anti Infect Ther 2005;3:797–804.PubMedCrossRefGoogle Scholar
  2. 2.
    Love C, Marwin SE, Palestro CJ. Nuclear medicine and the infected joint replacement. Semin Nucl Med 2009;39:66–78.PubMedCrossRefGoogle Scholar
  3. 3.
    Bauer TW, Parvizi J, Kobayashi N, Krebs V. Diagnosis of periprosthetic infection. J Bone Joint Surg Am 2006;88:869–82.PubMedCrossRefGoogle Scholar
  4. 4.
    Zimmerli W, Trampuz A, Ochsner PE. Prosthetic-joint infections. N Engl J Med 2004;351:1645–54.PubMedCrossRefGoogle Scholar
  5. 5.
    Berbari E, Mabry T, Tsaras G, Spangehl M, Erwin PJ, Murad MH, et al. Inflammatory blood laboratory levels as markers of prosthetic joint infection: a systematic review and meta-analysis. J Bone Joint Surg Am 2010;92:2102–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Parvizi J, Ghanem E, Menashe S, Barrack RL, Bauer TW. Periprosthetic infection: what are the diagnostic challenges? J Bone Joint Surg Am 2006;88 Suppl 4:138–47.PubMedCrossRefGoogle Scholar
  7. 7.
    Palestro CJ, Love C, Miller TT. Infection and musculoskeletal conditions: imaging of musculoskeletal infections. Best Pract Res Clin Rheumatol 2006;20:1197–218.PubMedCrossRefGoogle Scholar
  8. 8.
    Palestro CJ, Love C. Radionuclide imaging of musculoskeletal infection: conventional agents. Semin Musculoskelet Radiol 2007;11:335–52.PubMedCrossRefGoogle Scholar
  9. 9.
    Love C, Din AS, Tomas MB, Kalapparambath TP, Palestro CJ. Radionuclide bone imaging: an illustrative review. Radiographics 2003;23:341–58.PubMedCrossRefGoogle Scholar
  10. 10.
    Maurer AH, Chen DC, Camargo EE, Wong DF, Wagner Jr HN, Alderson PO. Utility of three-phase skeletal scintigraphy in suspected osteomyelitis: concise communication. J Nucl Med 1981;22:941–9.PubMedGoogle Scholar
  11. 11.
    Palestro CJ, Swyer AJ, Kim CK, Goldsmith SJ. Infected knee prosthesis: diagnosis with In-111 leukocyte, Tc-99m sulfur colloid, and Tc-99m MDP imaging. Radiology 1991;179:645–8.PubMedGoogle Scholar
  12. 12.
    Levitsky KA, Hozack WJ, Balderston RA, Rothman RH, Gluckman SJ, Maslack MM, et al. Evaluation of the painful prosthetic joint. Relative value of bone scan, sedimentation rate, and joint aspiration. J Arthroplasty 1991;6:237–44.PubMedCrossRefGoogle Scholar
  13. 13.
    Schauwecker DS. The scintigraphic diagnosis of osteomyelitis. AJR Am J Roentgenol 1992;158:9–18.PubMedGoogle Scholar
  14. 14.
    Itasaka T, Kawai A, Sato T, Mitani S, Inoue H. Diagnosis of infection after total hip arthroplasty. J Orthop Sci 2001;6:320–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Segura AB, Muñoz A, Brulles YR, Hernandez Hermoso JA, Díaz MC, Bajen Lazaro MT, et al. What is the role of bone scintigraphy in the diagnosis of infected joint prostheses? Nucl Med Commun 2004;25:527–32.PubMedCrossRefGoogle Scholar
  16. 16.
    Stumpe KD, Nötzli HP, Zanetti M, Kamel EM, Hany TF, Görres GW, et al. FDG PET for differentiation of infection and aseptic loosening in total hip replacements: comparison with conventional radiography and three-phase bone scintigraphy. Radiology 2004;231:333–41.PubMedCrossRefGoogle Scholar
  17. 17.
    Reinartz P, Mumme T, Hermanns B, Cremerius U, Wirtz DC, Schaefer WM, et al. Radionuclide imaging of the painful hip arthroplasty: positron-emission tomography versus triple-phase bone scanning. J Bone Joint Surg Br 2005;87:465–70.Google Scholar
  18. 18.
    Nagoya S, Kaya M, Sasaki M, Tateda K, Yamashita T. Diagnosis of peri-prosthetic infection at the hip using triple-phase bone scintigraphy. J Bone Joint Surg Br 2008;90:140–4.PubMedCrossRefGoogle Scholar
  19. 19.
    Gratz S, Höffken H, Kaiser JW, Behr TM, Strosche H, Reize P. Nuclear medical imaging in case of painful knee arthroplasty. Radiologe 2009;49:59–67.PubMedCrossRefGoogle Scholar
  20. 20.
    Magnuson JE, Brown ML, Hauser MF, Berquist TH, Fitzgerald Jr RH, Klee GG. In-111-labeled leukocyte scintigraphy in suspected orthopedic prosthesis infection: comparison with other imaging modalities. Radiology 1988;168:235–9.PubMedGoogle Scholar
  21. 21.
    Lieberman JR, Huo MH, Schneider R, Salvati EA, Rodi S. Evaluation of painful hip arthroplasties. Are technetium bone scans necessary? J Bone Joint Surg Br 1993;75:475–8.PubMedGoogle Scholar
  22. 22.
    Rosenthall L, Lisbona R, Hernandez M, Hadjipavlou A. 99mTc-PP and 67Ga imaging following insertion of orthopedic devices. Radiology 1979;133:717–21.PubMedGoogle Scholar
  23. 23.
    Schauwecker DS, Park HM, Mock BH, Burt RW, Kernick CB, Ruoff III AC, et al. Evaluation of complicating osteomyelitis with Tc-99m MDP, In-111 granulocytes, and Ga-67 citrate. J Nucl Med 1984;25:849–53.PubMedGoogle Scholar
  24. 24.
    Merkel KD, Brown ML, Fitzgerald Jr RH. Sequential technetium-99m HMDP-gallium-67 citrate imaging for the evaluation of infection in the painful prosthesis. J Nucl Med 1986;27:1413–7.PubMedGoogle Scholar
  25. 25.
    Palestro CJ. The current role of gallium imaging in infection. Semin Nucl Med 1994;24:128–41.PubMedCrossRefGoogle Scholar
  26. 26.
    Gómez-Luzuriaga MA, Galán V, Villar JM. Scintigraphy with Tc, Ga and In in painful total hip prostheses. Int Orthop 1988;12:163–7.PubMedCrossRefGoogle Scholar
  27. 27.
    Kraemer WJ, Saplys R, Waddell JP, Morton J. Bone scan, gallium scan, and hip aspiration in the diagnosis of infected total hip arthroplasty. J Arthroplasty 1993;8:611–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Thakur ML, Lavender JP, Arnot RN, Silvester DJ, Segal AW. Indium-111-labeled autologous leukocytes in man. J Nucl Med 1977;18:1014–21.PubMedGoogle Scholar
  29. 29.
    Peters AM, Danpure HJ, Osman S, Hawker RJ, Henderson BL, Hodgson HJ, et al. Clinical experience with 99mTc-hexamethylpropylene-amineoxime for labelling leucocytes and imaging inflammation. Lancet 1986;2:946–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Palestro CJ, Love C, Bhargava KK. Labeled leukocyte imaging: current status and future directions. Q J Nucl Med Mol Imaging 2009;53:105–23.PubMedGoogle Scholar
  31. 31.
    Love C, Tomas MB, Marwin SE, Pugliese PV, Palestro CJ. Role of nuclear medicine in diagnosis of the infected joint replacement. Radiographics 2001;21:1229–38.PubMedGoogle Scholar
  32. 32.
    Merkel KD, Brown ML, Dewanjee MK, Fitzgerald Jr RH. Comparison of indium-labeled-leukocyte imaging with sequential technetium-gallium scanning in the diagnosis of low-grade musculoskeletal sepsis. A prospective study. J Bone Joint Surg Am 1985;67:465–76.PubMedGoogle Scholar
  33. 33.
    Datz FL, Thorne DA. Effect of chronicity of infection on the sensitivity of the In-111-labeled leukocyte scan. AJR Am J Roentgenol 1986;147:809–12.PubMedGoogle Scholar
  34. 34.
    Krznaric E, Roo MD, Verbruggen A, Stuyck J, Mortelmans L. Chronic osteomyelitis: diagnosis with technetium-99m-d, l-hexamethylpropylene amine oxime labelled leucocytes. Eur J Nucl Med 1996;23:792–7.PubMedCrossRefGoogle Scholar
  35. 35.
    Larikka MJ, Ahonen AK, Junila JA, Niemelä O, Hämäläinen MM, Syrjälä HP. Extended combined 99mTc-white blood cell and bone imaging improves the diagnostic accuracy in the detection of hip replacement infections. Eur J Nucl Med 2001;28:288–93.PubMedCrossRefGoogle Scholar
  36. 36.
    Larikka MJ, Ahonen AK, Junila JA, Niemelä O, Hämäläinen MM, Syrjälä HP. Improved method for detecting knee replacement infections based on extended combined 99mTc-white blood cell/bone imaging. Nucl Med Commun 2001;22:1145–50.PubMedCrossRefGoogle Scholar
  37. 37.
    Datz FL, Thorne DA. Effect of antibiotic therapy on the sensitivity of indium-111-labeled leukocyte scans. J Nucl Med 1986;27:1849–53.PubMedGoogle Scholar
  38. 38.
    King AD, Peters AM, Stuttle AW, Lavender JP. Imaging of bone infection with labelled white blood cells: role of contemporaneous bone marrow imaging. Eur J Nucl Med 1990;17:148–51.PubMedCrossRefGoogle Scholar
  39. 39.
    Seabold JE, Nepola JV, Marsh JL, Hawes DR, Justin EP, Ponto JA, et al. Postoperative bone marrow alterations: potential pitfalls in the diagnosis of osteomyelitis with In-111-labeled leukocyte scintigraphy. Radiology 1991;180:741–7.PubMedGoogle Scholar
  40. 40.
    Palestro CJ, Roumanas P, Swyer AJ, Kim CK, Goldsmith SJ. Diagnosis of musculoskeletal infection using combined In-111 labeled leukocyte and Tc-99m SC marrow imaging. Clin Nucl Med 1992;17:269–73.PubMedCrossRefGoogle Scholar
  41. 41.
    Scher DM, Pak K, Lonner JH, Finkel JE, Zuckerman JD, Di Cesare PE. The predictive value of indium-111 leukocyte scans in the diagnosis of infected total hip, knee, or resection arthroplasties. J Arthroplasty 2000;15:295–300.PubMedCrossRefGoogle Scholar
  42. 42.
    Palestro CJ. Nuclear medicine, the painful prosthetic joint, and orthopedic infection. J Nucl Med 2003;44:927–9.PubMedGoogle Scholar
  43. 43.
    Reinartz P. FDG-PET in patients with painful hip and knee arthroplasty: technical breakthrough or just more of the same. Q J Nucl Med Mol Imaging 2009;53:41–50.PubMedGoogle Scholar
  44. 44.
    Johnson JA, Christie MJ, Sandler MP, Parks Jr PF, Homra L, Kaye JJ. Detection of occult infection following total joint arthroplasty using sequential technetium-99m HDP bone scintigraphy and indium-111 WBC imaging. J Nucl Med 1988;29:1347–53.PubMedGoogle Scholar
  45. 45.
    Teller RE, Christie MJ, Martin W, Nance EP, Haas DW. Sequential indium-labeled leukocyte and bone scans to diagnose prosthetic joint infection. Clin Orthop Relat Res 2000;373:241–7.PubMedCrossRefGoogle Scholar
  46. 46.
    Mulamba L, Ferrant A, Leners N, de Nayer P, Rombouts JJ, Vincent A. Indium-111 leucocyte scanning in the evaluation of painful hip arthroplasty. Acta Orthop Scand 1983;54:695–7.PubMedCrossRefGoogle Scholar
  47. 47.
    Palestro CJ, Kim CK, Swyer AJ, Capozzi JD, Solomon RW, Goldsmith SJ. Total-hip arthroplasty: periprosthetic indium-111-labeled leukocyte activity and complementary technetium-99m-sulfur colloid imaging in suspected infection. J Nucl Med 1990;31:1950–5.PubMedGoogle Scholar
  48. 48.
    Joseph TN, Mujtaba M, Chen AL, Maurer SL, Zuckerman JD, Maldjian C, et al. Efficacy of combined technetium-99m sulfur colloid/indium-111 leukocyte scans to detect infected total hip and knee arthroplasties. J Arthroplasty 2001;16:753–8.PubMedCrossRefGoogle Scholar
  49. 49.
    Love C, Marwin SE, Tomas MB, Krauss ES, Tronco GG, Bhargava KK, et al. Diagnosing infection in the failed joint replacement: a comparison of coincidence detection 18F-FDG and 111In-labeled leukocyte/99mTc-sulfur colloid marrow imaging. J Nucl Med 2004;45:1864–71.PubMedGoogle Scholar
  50. 50.
    El Espera I, Blondet C, Moullart V, Saidi L, Havet E, Mertl P, et al. The usefulness of 99mTc sulfur colloid bone marrow scintigraphy combined with 111In leucocyte scintigraphy in prosthetic joint infection. Nucl Med Commun 2004;25:171–5.PubMedCrossRefGoogle Scholar
  51. 51.
    Fuster D, Duch J, Soriano A, Garcia S, Setoain X, Bori G, et al. Potential use of bone marrow scintigraphy in suspected prosthetic hip infection evaluated with 99mTc-HMPAO-leukocytes. Rev Esp Med Nucl 2008;27:430–5.PubMedCrossRefGoogle Scholar
  52. 52.
    Fernandez P, Monet A, Matei C, De Clermont H, Guyot M, Jeandot R, et al. 99mTc-HMPAO labelled white blood cell scintigraphy in patients with osteoarticular infection: the value of late images for diagnostic accuracy and interobserver reproducibility. Eur J Clin Microbiol Infect Dis 2008;27:1239–44.PubMedCrossRefGoogle Scholar
  53. 53.
    Aktolun C, Ussov WY, Arka A, Glass D, Gunasekera RD, Peters AM. Technetium-99m and indium-111 double labelling of granulocytes for kinetic and clinical studies. Eur J Nucl Med 1995;22:330–4.PubMedCrossRefGoogle Scholar
  54. 54.
    Dutton JA, Bird NJ, Skehan SJ, Peters AM. Evaluation of a 3-hour indium-111 leukocyte image as a surrogate for a technetium-99m nanocolloid marrow scan in the diagnosis of orthopedic infection. Clin Nucl Med 2004;29:469–74.PubMedCrossRefGoogle Scholar
  55. 55.
    Pelosi E, Baiocco C, Pennone M, Migliaretti G, Varetto T, Maiello A, et al. 99mTc-HMPAO-leukocyte scintigraphy in patients with symptomatic total hip or knee arthroplasty: improved diagnostic accuracy by means of semiquantitative evaluation. J Nucl Med 2004;45:438–44.PubMedGoogle Scholar
  56. 56.
    Simonsen L, Buhl A, Oersnes T, Duus B. White blood cell scintigraphy for differentiation of infection and aseptic loosening: a retrospective study of 76 painful hip prostheses. Acta Orthop 2007;78:640–7.PubMedCrossRefGoogle Scholar
  57. 57.
    Meller J, Liersch T, Oezerden MM, Sahlmann CO, Meller B. Targeting NCA-95 and other granulocyte antigens and receptors with radiolabeled monoclonal antibodies (Mabs). Q J Nucl Med Mol Imaging 2010;54:582–98.PubMedGoogle Scholar
  58. 58.
    Hotze AL, Briele B, Overbeck B, Kropp J, Gruenwald F, Mekkawy MA, et al. Technetium-99m-labeled anti-granulocyte antibodies in suspected bone infections. J Nucl Med 1992;33:526–31.PubMedGoogle Scholar
  59. 59.
    Boubaker A, Delaloye AB, Blanc CH, Dutoit M, Leyvraz PF, Delaloye B. Immunoscintigraphy with antigranulocyte monoclonal antibodies for the diagnosis of septic loosening of hip prostheses. Eur J Nucl Med 1995;22:139–47.PubMedCrossRefGoogle Scholar
  60. 60.
    Devillers A, Garin E, Polard JL, Poirier JY, Arvieux C, Girault S, et al. Comparison of Tc-99m-labelled antileukocyte fragment Fab′ and Tc-99m-HMPAO leukocyte scintigraphy in the diagnosis of bone and joint infections: a prospective study. Nucl Med Commun 2000;21:747–53.PubMedCrossRefGoogle Scholar
  61. 61.
    Ryan PJ. Leukoscan for orthopaedic imaging in clinical practice. Nucl Med Commun 2002;23:707–14.PubMedCrossRefGoogle Scholar
  62. 62.
    Vicente AG, Almoguera M, Alonso JC, Heffernan AJ, Gomez A, Contreras PI, et al. Diagnosis of orthopedic infection in clinical practice using Tc-99m sulesomab (antigranulocyte monoclonal antibody fragment Fab′2). Clin Nucl Med 2004;29:781–5.PubMedCrossRefGoogle Scholar
  63. 63.
    Pakos EE, Trikalinos TA, Fotopoulos AD, Ioannidis JP. Prosthesis infection: diagnosis after total joint arthroplasty with antigranulocyte scintigraphy with 99mTc-labeled monoclonal antibodies–a meta-analysis. Radiology 2007;242:101–8.PubMedCrossRefGoogle Scholar
  64. 64.
    Klett R, Kordelle J, Stahl U, Khalisi A, Puille M, Steiner D, et al. Immunoscintigraphy of septic loosening of knee endoprosthesis: a retrospective evaluation of the antigranulocyte antibody BW 250/183. Eur J Nucl Med Mol Imaging 2003;30:1463–6.PubMedCrossRefGoogle Scholar
  65. 65.
    Rubello D, Casara D, Maran A, Avogaro A, Tiengo A, Muzzio PC. Role of anti-granulocyte Fab′ fragment antibody scintigraphy (LeukoScan) in evaluating bone infection: acquisition protocol, interpretation criteria and clinical results. Nucl Med Commun 2004;25:39–47.PubMedCrossRefGoogle Scholar
  66. 66.
    Gratz S, Behr TM, Reize P, Pfestroff A, Kampen WU, Höffken H. (99m)Tc-Fab′ fragments (sulesomab) for imaging septically loosened total knee arthroplasty. J Int Med Res 2009;37:54–67.PubMedGoogle Scholar
  67. 67.
    Sousa R, Massada M, Pereira A, Fontes F, Amorim I, Oliveira A. Diagnostic accuracy of combined 99mTc-sulesomab and 99mTc-nanocolloid bone marrow imaging in detecting prosthetic joint infection. Nucl Med Commun 2011;32:834–9.PubMedCrossRefGoogle Scholar
  68. 68.
    Mariani G, Bruselli L, Kuwert T, Kim EE, Flotats A, Israel O, et al. A review on the clinical uses of SPECT/CT. Eur J Nucl Med Mol Imaging 2010;37:1959–85.PubMedCrossRefGoogle Scholar
  69. 69.
    Weon YC, Yang SO, Choi YY, Shin JW, Ryu JS, Shin MJ, et al. Use of Tc-99m HMPAO leukocyte scans to evaluate bone infection: incremental value of additional SPECT images. Clin Nucl Med 2000;25:519–26.PubMedCrossRefGoogle Scholar
  70. 70.
    Van Acker F, Nuyts J, Maes A, Vanquickenborne B, Stuyck J, Bellemans J, et al. FDG-PET, 99mtc-HMPAO white blood cell SPET and bone scintigraphy in the evaluation of painful total knee arthroplasties. Eur J Nucl Med 2001;28:1496–504.PubMedCrossRefGoogle Scholar
  71. 71.
    Vanquickenborne B, Maes A, Nuyts J, Van AF, Stuyck J, Mulier M, et al. The value of (18)FDG-PET for the detection of infected hip prosthesis. Eur J Nucl Med Mol Imaging 2003;30:705–15.PubMedCrossRefGoogle Scholar
  72. 72.
    Bar-Shalom R, Yefremov N, Guralnik L, Keidar Z, Engel A, Nitecki S, et al. SPECT/CT using 67Ga and 111In-labeled leukocyte scintigraphy for diagnosis of infection. J Nucl Med 2006;47:587–94.PubMedGoogle Scholar
  73. 73.
    Schillaci O. Hybrid imaging systems in the diagnosis of osteomyelitis and prosthetic joint infection. Q J Nucl Med Mol Imaging 2009;53:95–104.PubMedGoogle Scholar
  74. 74.
    Bunyaviroch T, Aggarwal A, Oates ME. Optimized scintigraphic evaluation of infection and inflammation: role of single-photon emission computed tomography/computed tomography fusion imaging. Semin Nucl Med 2006;36:295–311.PubMedCrossRefGoogle Scholar
  75. 75.
    Horger M, Eschmann SM, Pfannenberg C, Storek D, Dammann F, Vonthein R, et al. The value of SPET/CT in chronic osteomyelitis. Eur J Nucl Med Mol Imaging 2003;30:1665–73.PubMedCrossRefGoogle Scholar
  76. 76.
    Filippi L, Schillaci O. Usefulness of hybrid SPECT/CT in 99mTc-HMPAO-labeled leukocyte scintigraphy for bone and joint infections. J Nucl Med 2006;47:1908–13.PubMedGoogle Scholar
  77. 77.
    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;21:247–57.PubMedCrossRefGoogle Scholar
  78. 78.
    Guhlmann A, Brecht-Krauss D, Suger G, Glatting G, Kotzerke J, Kinzl L, et al. Chronic osteomyelitis: detection with FDG PET and correlation with histopathologic findings. Radiology 1998;206:749–54.PubMedGoogle Scholar
  79. 79.
    de Winter F, van de Wiele C, Vogelaers D, de Smet K, Verdonk R, Dierckx RA. Fluorine-18 fluorodeoxyglucose-position emission tomography: a highly accurate imaging modality for the diagnosis of chronic musculoskeletal infections. J Bone Joint Surg Am 2001;83-A:651–60.PubMedGoogle Scholar
  80. 80.
    Zhuang H, Yang H, Alavi A. Critical role of 18F-labeled fluorodeoxyglucose PET in the management of patients with arthroplasty. Radiol Clin North Am 2007;45:711–8. vii.PubMedCrossRefGoogle Scholar
  81. 81.
    Zhuang H, Duarte PS, Pourdehnad M, Maes A, Van Acker F, Shnier D, et al. The promising role of 18F-FDG PET in detecting infected lower limb prosthesis implants. J Nucl Med 2001;42:44–8.PubMedGoogle Scholar
  82. 82.
    Zhuang H, Chacko TK, Hickeson M, Stevenson K, Feng Q, Ponzo F, et al. Persistent non-specific FDG uptake on PET imaging following hip arthroplasty. Eur J Nucl Med Mol Imaging 2002;29:1328–33.PubMedCrossRefGoogle Scholar
  83. 83.
    Delank KS, Schmidt M, Michael JW, Dietlein M, Schicha H, Eysel P. The implications of 18F-FDG PET for the diagnosis of endoprosthetic loosening and infection in hip and knee arthroplasty: results from a prospective, blinded study. BMC Musculoskelet Disord 2006;7:20.PubMedCrossRefGoogle Scholar
  84. 84.
    Stumpe KD, Romero J, Ziegler O, Kamel EM, von Schulthess GK, Strobel K, et al. The value of FDG-PET in patients with painful total knee arthroplasty. Eur J Nucl Med Mol Imaging 2006;33:1218–25.PubMedCrossRefGoogle Scholar
  85. 85.
    Pill SG, Parvizi J, Tang PH, Garino JP, Nelson C, Zhuang H, et al. Comparison of fluorodeoxyglucose positron emission tomography and (111)indium-white blood cell imaging in the diagnosis of periprosthetic infection of the hip. J Arthroplasty 2006;21:91–7.PubMedCrossRefGoogle Scholar
  86. 86.
    García-Barrecheguren E, Rodríguez FM, Toledo Santana G, Valentí Nín JR, Richter Echevarría JA FDG-PET: a new diagnostic approach in hip prosthetic replacement. Rev Esp Med Nucl 2007;26:208–20.PubMedCrossRefGoogle Scholar
  87. 87.
    Kumar V. Radiolabeled white blood cells and direct targeting of micro-organisms for infection imaging. Q J Nucl Med Mol Imaging 2005;49:325–38.PubMedGoogle Scholar
  88. 88.
    Bleeker-Rovers CP, Rennen HJ, Boerman OC, Wymenga AB, Visser EP, Bakker JH, et al. 99mTc-labeled interleukin 8 for the scintigraphic detection of infection and inflammation: first clinical evaluation. J Nucl Med 2007;48:337–43.PubMedGoogle Scholar
  89. 89.
    Hnatowich DJ, Virzi F, Rusckowski M. Investigations of avidin and biotin for imaging applications. J Nucl Med 1987;28:1294–302.PubMedGoogle Scholar
  90. 90.
    Shoup TM, Fischman AJ, Jaywook S, Babich JW, Strauss HW, Elmaleh DR. Synthesis of fluorine-18-labeled biotin derivatives: biodistribution and infection localization. J Nucl Med 1994;35:1685–90.PubMedGoogle Scholar
  91. 91.
    Erba PA, Cataldi AG, Tascini C, Leonildi A, Manfredi C, Mariani G, et al. 111In-DTPA-Biotin uptake by Staphylococcus aureus. Nucl Med Commun 2010;31:994–7.PubMedCrossRefGoogle Scholar
  92. 92.
    Lazzeri E, Erba P, Perri M, Tascini C, Doria R, Giorgetti J, et al. Scintigraphic imaging of vertebral osteomyelitis with 111in-biotin. Spine (Phila Pa 1976) 2008;33:E198–204.CrossRefGoogle Scholar
  93. 93.
    Lorberboym M, Feldbrin Z, Hendel D, Blankenberg FG, Schachter P. The use of 99mTc-recombinant human annexin V imaging for differential diagnosis of aseptic loosening and low-grade infection in hip and knee prostheses. J Nucl Med 2009;50:534–7.PubMedCrossRefGoogle Scholar
  94. 94.
    Buscombe JR. The future of infection imaging. Q J Nucl Med Mol Imaging 2006;50:99–103.PubMedGoogle Scholar
  95. 95.
    Vinjamuri S, Hall AV, Solanki KK, Bomanji J, Siraj Q, O’Shaughnessy E, et al. Comparison of 99mTc infecton imaging with radiolabelled white-cell imaging in the evaluation of bacterial infection. Lancet 1996;347:233–5.PubMedCrossRefGoogle Scholar
  96. 96.
    Sonmezoglu K, Sonmezoglu M, Halac M, Akgün I, Türkmen C, Onsel C, et al. Usefulness of 99mTc-ciprofloxacin (infecton) scan in diagnosis of chronic orthopedic infections: comparative study with 99mTc-HMPAO leukocyte scintigraphy. J Nucl Med 2001;42:567–74.PubMedGoogle Scholar
  97. 97.
    Larikka MJ, Ahonen AK, Niemelä O, Junila JA, Hämäläinen MM, Britton K, et al. Comparison of 99mTc ciprofloxacin, 99mTc white blood cell and three-phase bone imaging in the diagnosis of hip prosthesis infections: improved diagnostic accuracy with extended imaging time. Nucl Med Commun 2002;23:655–61.PubMedCrossRefGoogle Scholar
  98. 98.
    Larikka MJ, Ahonen AK, Niemelä O, Puronto O, Junila JA, Hämäläinen MM, et al. 99m Tc-ciprofloxacin (Infecton) imaging in the diagnosis of knee prosthesis infections. Nucl Med Commun 2002;23:167–70.PubMedCrossRefGoogle Scholar
  99. 99.
    Sarda L, Saleh-Mghir A, Peker C, Meulemans A, Crémieux AC, Le Guludec D. Evaluation of (99m)Tc-ciprofloxacin scintigraphy in a rabbit model of Staphylococcus aureus prosthetic joint infection. J Nucl Med 2002;43:239–45.PubMedGoogle Scholar
  100. 100.
    Dumarey N, Blocklet D, Appelboom T, Tant L, Schoutens A. Infecton is not specific for bacterial osteo-articular infective pathology. Eur J Nucl Med Mol Imaging 2002;29:530–5.PubMedCrossRefGoogle Scholar
  101. 101.
    Sarda L, Crémieux AC, Lebellec Y, Meulemans A, Lebtahi R, Hayem G, et al. Inability of 99mTc-ciprofloxacin scintigraphy to discriminate between septic and sterile osteoarticular diseases. J Nucl Med 2003;44:920–6.PubMedGoogle Scholar
  102. 102.
    Langer O, Brunner M, Zeitlinger M, Ziegler S, Müller U, Dobrozemsky G, et al. In vitro and in vivo evaluation of [18F]ciprofloxacin for the imaging of bacterial infections with PET. Eur J Nucl Med Mol Imaging 2005;32:143–50.PubMedCrossRefGoogle Scholar
  103. 103.
    Fuster D, Soriano A, Garcia S, Piera C, Suades J, Rodríguez D, et al. Usefulness of 99mTc-ciprofloxacin scintigraphy in the diagnosis of prosthetic joint infections. Nucl Med Commun 2011;32:44–51.PubMedCrossRefGoogle Scholar
  104. 104.
    Nibbering PH, Welling MM, van den Broek PJ, van Wyngaarden KE, Pauwels EK, Calame W. Radiolabelled antimicrobial peptides for imaging of infections: a review. Nucl Med Commun 1998;19:1117–21.PubMedCrossRefGoogle Scholar
  105. 105.
    Lupetti A, Welling MM, Pauwels EK, Nibbering PH. Radiolabelled antimicrobial peptides for infection detection. Lancet Infect Dis 2003;3:223–9.PubMedCrossRefGoogle Scholar
  106. 106.
    Welling MM, Lupetti A, Balter HS, Lanzzeri S, Souto B, Rey AM, et al. 99mTc-labeled antimicrobial peptides for detection of bacterial and Candida albicans infections. J Nucl Med 2001;42:788–94.PubMedGoogle Scholar
  107. 107.
    Nibbering PH, Welling MM, Paulusma-Annema A, Brouwer CP, Lupetti A, Pauwels EK. 99mTc-Labeled UBI 29-41 peptide for monitoring the efficacy of antibacterial agents in mice infected with Staphylococcus aureus. J Nucl Med 2004;45:321–6.PubMedGoogle Scholar
  108. 108.
    Sarda-Mantel L, Saleh-Mghir A, Welling MM, Meulemans A, Vrigneaud JM, Raguin O, et al. Evaluation of 99mTc-UBI 29-41 scintigraphy for specific detection of experimental Staphylococcus aureus prosthetic joint infections. Eur J Nucl Med Mol Imaging 2007;34:1302–9.PubMedCrossRefGoogle Scholar
  109. 109.
    Akhtar MS, Khan ME, Khan B, Irfanullah J, Afzal MS, Khan MA, et al. An imaging analysis of (99m)Tc-UBI (29-41) uptake in S. aureus infected thighs of rabbits on ciprofloxacin treatment. Eur J Nucl Med Mol Imaging 2008;35:1056–64.PubMedCrossRefGoogle Scholar
  110. 110.
    Salber D, Gunawan J, Langen KJ, Fricke E, Klauth P, Burchert W, et al. Comparison of 99mTc- and 18F-ubiquicidin autoradiography to anti-Staphylococcus aureus immunofluorescence in rat muscle abscesses. J Nucl Med 2008;49:995–9.PubMedCrossRefGoogle Scholar
  111. 111.
    Brouwer CP, Gemmel FF, Welling MM. Evaluation of 99mTc-UBI 29-41 scintigraphy for specific detection of experimental multidrug-resistant Staphylococcus aureus bacterial endocarditis. Q J Nucl Med Mol Imaging 2010;54:442–50.PubMedGoogle Scholar
  112. 112.
    Arteaga de Murphy C, Gemmel F, Balter J. Clinical trial of specific imaging of infections. Nucl Med Commun 2010;31:726–33.CrossRefGoogle Scholar
  113. 113.
    Rusckowski M, Gupta S, Liu G, Dou S, Hnatowich DJ. Investigations of a (99m)Tc-labeled bacteriophage as a potential infection-specific imaging agent. J Nucl Med 2004;45:1201–8.PubMedGoogle Scholar
  114. 114.
    Rusckowski M, Gupta S, Liu G, Dou S, Hnatowich DJ. Investigation of four (99m)Tc-labeled bacteriophages for infection-specific imaging. Nucl Med Biol 2008;35:433–40.PubMedCrossRefGoogle Scholar
  115. 115.
    Diaz Jr LA, Foss CA, Thornton K, Nimmagadda S, Endres CJ, Uzuner O, et al. Imaging of musculoskeletal bacterial infections by [124I]FIAU-PET/CT. PLoS One 2007;2:e1007.PubMedCrossRefGoogle Scholar
  116. 116.
    Lazzeri E, Erba P, Perri M, Doria R, Tascini C, Mariani G. Clinical impact of SPECT/CT with In-111 biotin on the management of patients with suspected spine infection. Clin Nucl Med 2010;35:12–7.PubMedCrossRefGoogle Scholar
  117. 117.
    Graute V, Feist M, Lehner S, Haug A, Müller PE, Bartenstein P, et al. Detection of low-grade prosthetic joint infections using 99mTc-antigranulocyte SPECT/CT: initial clinical results. Eur J Nucl Med Mol Imaging 2010;37:1751–9.PubMedCrossRefGoogle Scholar
  118. 118.
    Chen SH, Ho KC, Hsieh PH, Lee MS, Yen TC. Potential clinical role of 18F FDG-PET/CT in detecting hip prosthesis infection: a study in patients undergoing two-stage revision arthroplasty with an interim spacer. Q J Nucl Med Mol Imaging 2010;54:429–35.PubMedGoogle Scholar
  119. 119.
    Dumarey N, Egrise D, Blocklet D, Stallenberg B, Remmelink M, del Marmol V, et al. Imaging infection with 18F-FDG-labeled leukocyte PET/CT: initial experience in 21 patients. J Nucl Med 2006;47:625–32.PubMedGoogle Scholar
  120. 120.
    Rini JN, Palestro CJ. Imaging of infection and inflammation with 18F-FDG-labeled leukocytes. Q J Nucl Med Mol Imaging 2006;50:143–6.PubMedGoogle Scholar
  121. 121.
    Rini JN, Bhargava KK, Tronco GG, Singer C, Caprioli R, Marwin SE, et al. PET with FDG-labeled leukocytes versus scintigraphy with 111In-oxine-labeled leukocytes for detection of infection. Radiology 2006;238:978–87.PubMedCrossRefGoogle Scholar
  122. 122.
    Bhargava KK, Gupta RK, Nichols KJ, Palestro CJ. In vitro human leukocyte labeling with (64)Cu: an intraindividual comparison with (111)In-oxine and (18)F-FDG. Nucl Med Biol 2009;36:545–9.PubMedCrossRefGoogle Scholar
  123. 123.
    Sterner T, Pink R, Freudenberg L, Jentzen T, Quitmann H, Bockisch A, et al. The role of [18F]fluoride positron emission tomography in the early detection of aseptic loosening of total knee arthroplasty. Int J Surg 2007;5:99–104.PubMedCrossRefGoogle Scholar
  124. 124.
    Kobayashi N, Inaba Y, Choe H, Ike H, Fujimaki H, Tezuka T, et al. Use of F-18 fluoride PET to differentiate septic from aseptic loosening in total hip arthroplasty patients. Clin Nucl Med 2011;36:e156–61.PubMedCrossRefGoogle Scholar
  125. 125.
    Kropholler MA, Boellaard R, Elzinga EH, van der Laken CJ, Maruyama K, Kloet RW, et al. Quantification of (R)-[11C]PK11195 binding in rheumatoid arthritis. Eur J Nucl Med Mol Imaging 2009;36:624–31.PubMedCrossRefGoogle Scholar
  126. 126.
    Mäkinen TJ, Lankinen P, Pöyhönen T, Jalava J, Aro HT, Roivainen A. Comparison of 18F-FDG and 68Ga PET imaging in the assessment of experimental osteomyelitis due to Staphylococcus aureus. Eur J Nucl Med Mol Imaging 2005;32:1259–68.PubMedCrossRefGoogle Scholar
  127. 127.
    Lankinen P, Mäkinen TJ, Pöyhönen TA, Virsu P, Salomäki S, Hakanen AJ, et al. (68)Ga-DOTAVAP-P1 PET imaging capable of demonstrating the phase of inflammation in healing bones and the progress of infection in osteomyelitic bones. Eur J Nucl Med Mol Imaging 2008;35:352–64.PubMedCrossRefGoogle Scholar
  128. 128.
    Ujula T, Salomäki S, Virsu P, Lankinen P, Mäkinen TJ, Autio A, et al. Synthesis, 68Ga labeling and preliminary evaluation of DOTA peptide binding vascular adhesion protein-1: a potential PET imaging agent for diagnosing osteomyelitis. Nucl Med Biol 2009;36:631–41.PubMedCrossRefGoogle Scholar
  129. 129.
    Kwee TC, Kwee RM, Alavi A. FDG-PET for diagnosing prosthetic joint infection: systematic review and metaanalysis. Eur J Nucl Med Mol Imaging 2008;35:2122–32.PubMedCrossRefGoogle Scholar
  130. 130.
    van der Bruggen W, Bleeker-Rovers CP, Boerman OC, Gotthardt M, Oyen WJ. PET and SPECT in osteomyelitis and prosthetic bone and joint infections: a systematic review. Semin Nucl Med 2010;40:3–15.PubMedCrossRefGoogle Scholar
  131. 131.
    Gemmel F, Dumarey N, Welling M. Future diagnostic agents. Semin Nucl Med 2009;39:11–26.PubMedCrossRefGoogle Scholar
  132. 132.
    Del Pozo JL, Patel R. Infection associated with prosthetic joints. N Engl J Med 2009;361:787–94.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Filip Gemmel
    • 1
  • Hans Van den Wyngaert
    • 2
  • Charito Love
    • 3
  • M. M. Welling
    • 4
  • Paul Gemmel
    • 5
  • Christopher J. Palestro
    • 6
  1. 1.Department of Nuclear MedicineAZ Alma Campus SijseleSijsele-DammeBelgium
  2. 2.Department of Orthopaedic SurgeryAZ Alma Campus SijseleSijsele-DammeBelgium
  3. 3.Division of Nuclear Medicine and RadiologyAlbert Einstein College of Medicine of Yeshiva UniversityBronxUSA
  4. 4.Scientist Molecular Imaging, Department of Radiology, Section of Nuclear Medicine C2-203Leiden University Medical CenterLeidenThe Netherlands
  5. 5.The Faculty of Economics and Business AdministrationGhent UniversityGhentBelgium
  6. 6.Division of Nuclear Medicine and Molecular Imaging, Department of RadiologyHofstra North Shore-Long Island Jewish Health SystemHempsteadUSA

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