Skip to main content

Advertisement

SpringerLink
Log in

Clinical feasibility of two-step streptavidin/111In-biotin scintigraphy in patients with suspected vertebral osteomyelitis

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Streptavidin accumulates at sites of inflammation and infection as a result of increased capillary permeability. In addition to being utilised by bacteria for their own growth, biotin forms a stable, high-affinity non-covalent complex with avidin. The objective of this investigation was to determine the diagnostic performance of two-step streptavidin/111In-biotin imaging for evaluating patients with suspected vertebral osteomyelitis.

Methods

We evaluated 55 consecutive patients with suspected vertebral osteomyelitis (34 women and 21 men aged 27–86 years), within 2 weeks after the onset of clinical symptoms. Thirty-two of the patients underwent magnetic resonance imaging (MRI) and 24, computed tomography (CT). DTPA-conjugated biotin was radiolabelled by incubating 500 μg of DTPA-biotin with 111 MBq of 111In-chloride. Two-step scintigraphy was performed by first infusing 3 mg streptavidin intravenously, followed 4 h later by 111In-biotin. Imaging was begun 60 min later.

Results

Streptavidin/111In-biotin scintigraphy was positive in 32/34 patients with spinal infection (94.12% sensitivity). The study was negative in 19/21 patients without infection (95.24% specificity). The corresponding results for MRI and CT were 54.17% and 35.29% (sensitivity), and 75% and 57.14% (specificity), respectively. All statistical parameters of diagnostic performance (Youden’s J index, kappa measure of agreement with correct classification, accuracy, sensitivity, specificity, positive likelihood and negative likelihood) were clearly better for streptavidin/111In-biotin scintigraphy than for either MRI or CT.

Conclusion

Streptavidin/111In-biotin scintigraphy is highly sensitive and specific for detecting vertebral osteomyelitis in the first 2 weeks after the onset of clinical symptoms, and is potentially very useful for guiding clinical decisions on instituting appropriate therapy.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1a–f
Fig. 2

Similar content being viewed by others

References

  1. Eismont FJ, Bohlman HH, Soni PL, Goldberg VM, Freeafer AA. Pyogenic and fungal vertebral osteomyelitis with paralysis. J Bone Joint Surg 1983;65A:19–29

    Google Scholar 

  2. Enzmann DR. Infection and inflammation. In: Enzmann DR, DeLaPaz RL, Rubin JB, eds. Magnetic resonance of the spine. St. Louis: Mosby; 1990:260–300

  3. Wolansky LJ, Heary RF, Patterson T, Friedenberg JS, Tholany J, Chen JK, Patel N, Doddakashi S. Pseudosparing of the endplate: a potential pitfall in using MR imaging to diagnose infectious spondylitis. AJR 1999;172:777–780

    CAS  PubMed  Google Scholar 

  4. Wagner SC, Schweitzer ME, Morrison WB, Przybylski GJ, Parker L. Can imaging findings help differentiate spinal neuropathic arthropathy from disk space infection? Initial experience. Radiology 2000;214:693–699

    CAS  PubMed  Google Scholar 

  5. Carragee EJ. Pyogenic vertebral osteomyelitis. J Bone Joint Surg Am 1997;79:874–880

    Article  CAS  PubMed  Google Scholar 

  6. McHenry MC, Easley KA, Locker GA. Vertebral osteomyelitis: long-term outcome for 253 patients from 7 Cleveland-area hospitals. Clin Infect Dis 2002;34:1342–1350

    Article  PubMed  Google Scholar 

  7. Handmaker H, Leonards R. The bone scan in inflammatory osseous disease. Semin Nucl Med 1976;6:95–105

    CAS  PubMed  Google Scholar 

  8. Maurer AH, Chen DCP, Camargo EE, Wong DF, Wagner HN Jr, Alderson PO. Utility of three-phase skeletal scintigraphy in suspected osteomyelitis: concise communication. J Nucl Med 1981;22:941–949

    CAS  PubMed  Google Scholar 

  9. Ruther W, Hotze A, Moller F, Bockisch A, Heitzmann P, Biersack HJ. Diagnosis of bone and joint infection by leucocyte scintigraphy. A comparative study with 99mTc-HMPAO-labelled leucocytes, 99mTc-labelled antigranulocyte antibodies and 99mTc-labelled nano-colloid. Arch Orthop Trauma Surg 1990;110:26–32

    CAS  PubMed  Google Scholar 

  10. Hotze AL, Briele B, Overbeck B, Kropp J, Gruenwald F, Mekkawy MA, von Smekal A, Moeller F, Biersack HJ. Technetium-99m-labeled anti-granulocyte antibodies in suspected bone infections. J Nucl Med 1992;33:526–531

    CAS  PubMed  Google Scholar 

  11. Gratz S, Braun HG, Behr TM, Meller J, Herrmann A, Conrad M, Rathmann D, Bertagnoli R, Willert HG, Becker W. Photopenia in chronic vertebral osteomyelitis with technetium-99m-antigranulocyte antibody (BW 250/183). J Nucl Med 1997;38:211–216

    CAS  PubMed  Google Scholar 

  12. Boerman OC, Rennen H, Oyen WJ, Corstens FH. Radiopharmaceuticals to image infection and inflammation. Semin Nucl Med 2000;31:286–295

    Google Scholar 

  13. Turpin S, Lambert R. Role of scintigraphy in musculoskeletal and spinal infections. Radiol Clin North Am 2001;39:169–189

    CAS  PubMed  Google Scholar 

  14. Okarvi SM. Recent developments in 99mTc-labelled peptide-based radiopharmaceuticals: an overview. Nucl Med Commun 1999;20:1093–1112

    CAS  PubMed  Google Scholar 

  15. Welling MM, Paulusma-Annema A, Balter HS, Pauwels EK, Nibbering PH. Technetium-99m labelled antimicrobial peptides discriminate between bacterial infections and sterile inflammations. Eur J Nucl Med 2000;27:292–301

    Article  CAS  PubMed  Google Scholar 

  16. Kalicke T, Schmitz A, Risse JH, Arens S, Keller E, Hansis M, Schmitt O, Biersack HJ, Grunwald F. Fluorine-18 fluorodeoxyglucose PET in infectious bone diseases: results of histologically confirmed cases. Eur J Nucl Med 2000;27:524–528

    Article  CAS  PubMed  Google Scholar 

  17. Stumpe KD, Dazzi H, Schaffner A, von Schulthess GK. Infection imaging using whole-body FDG-PET. Eur J Nucl Med 2000;27:822–832

    Article  CAS  PubMed  Google Scholar 

  18. Rennen HJ, Corstens FH, Oyen WJ, Boerman OC. New concepts in infection/inflammation imaging. Q J Nucl Med 2001;45:167–173

    CAS  PubMed  Google Scholar 

  19. Signore A, Annovazzi A, Chianelli M, Corsetti F, Van de Wiele C, Waterhouse RN. Peptide radiopharmaceuticals for diagnosis and therapy. Eur J Nucl Med 2001;28:1555–1565

    Article  CAS  PubMed  Google Scholar 

  20. Zhuang H, Alavi A. 18-Fluorodeoxyglucose positron emission tomographic imaging in the detection and monitoring of infection and inflammation. Semin Nucl Med 2002;32:47–59

    PubMed  Google Scholar 

  21. Devillers A, Moisan A, Jean S, Arvieux C, Bourguet P. Technetium-99m hexamethyl-propylene amine oxime leucocyte scintigraphy for the diagnosis of bone and joint infections: a retrospective study in 116 patients. Eur J Nucl Med 1995;22:302–307

    CAS  PubMed  Google Scholar 

  22. Palestro CJ, Torres MA. Radionuclide imaging in orthopedic infections. Semin Nucl Med 1997;27:334–345

    CAS  PubMed  Google Scholar 

  23. Coleman RE, Welch D. Possible pitfalls with clinical imaging of indium-111 leukocytes. J Nucl Med 1980;21:122–125

    CAS  PubMed  Google Scholar 

  24. Mok YP, Carney WH, Fernandez-Ulloa M. Skeletal photopenic lesions in In-111 WBC imaging. J Nucl Med 1984;25:1322–1326

    CAS  PubMed  Google Scholar 

  25. Fernandex-Ulloa M, Vasavada PJ, Hanslits ML, Volarich DT, Elgazzar AH. Diagnosis of vertebral osteomyelitis: clinical, radiological and scintigraphic features. Orthopedics 1985;8:1144–1150

    PubMed  Google Scholar 

  26. Datz FL, Thorne DA. Cause and significance of cold bone defects on indium-111-labeled leukocyte imaging. J Nucl Med 1987;28:820–823

    CAS  PubMed  Google Scholar 

  27. Palestro CJ, Kim CK, Swyer AJ, Vallabhajosula S, Goldsmith SJ. Radionuclide diagnosis of vertebral osteomyelitis: indium-111-leukocyte and technetium-99m-methylene diphosphonate bone scintigraphy. J Nucl Med 1991;32:1861–1865

    CAS  PubMed  Google Scholar 

  28. Whalen JL, Brown ML, McLeod R, Fitzgerald RH Jr. Limitations of indium leukocyte imaging for the diagnosis of spine infections. Spine 1991;16:193–197

    CAS  PubMed  Google Scholar 

  29. Jacobson AF, Gilles CP, Cerqueira MD. Photopenic defects in marrow-containing skeleton on indium-111 leucocyte scintigraphy: prevalence at sites suspected of osteomyelitis and as an incidental finding. Eur J Nucl Med 1992;19:858–864

    CAS  PubMed  Google Scholar 

  30. Even-Sapir E, Martin RH. Degenerative disc disease. A cause for diagnostic dilemma on In-111 WBC studies in suspected osteomyelitis. Clin Nucl Med 1994;19:388–392

    CAS  PubMed  Google Scholar 

  31. Roelants V, Tang T, Ide C, Laloux P. Cold vertebra on 111In-white blood cell scintigraphy. Semin Nucl Med 2002;32:236–237

    Article  CAS  PubMed  Google Scholar 

  32. Gratz S, Dorner J, Oestmann JW, Opitz M, Behr T, Meller J, Grabbe E, Becker W. 67Ga-citrate and 99mTc-MDP for estimating the severity of vertebral osteomyelitis. Nucl Med Commun 2000;21:111–120

    Article  CAS  PubMed  Google Scholar 

  33. Love C, Patel M, Lonner BS, Tomas MB, Palestro CJ. Diagnosing spinal osteomyelitis: a comparison of bone and Ga-67 scintigraphy and magnetic resonance imaging. Clin Nucl Med 2000;25:963–977

    Article  CAS  PubMed  Google Scholar 

  34. Rusckowski M, Fritz B, Hnatowich DJ. Localization of infection using streptavidin and biotin: an alternative to nonspecific polyclonal immunoglobulin. J Nucl Med 1992;33:1810–1815

    CAS  PubMed  Google Scholar 

  35. Chiesa R, Melissano G, Castellano R, Fernandez Zamora C, Astore D, Samuel A, Paganelli G, Fazio F, Grossi A. Avidin and 111In-labelled biotin scan: a new radioisotopic method for localising vascular graft infections. Eur J Endovasc Surg 1995;10:405–414

    CAS  Google Scholar 

  36. Rusckowski M, Paganelli G, Hnatowich DJ, Magnani P, Virzi F, Fogarasi M, DiLeo C, Sudati F, Fazio F. Imaging osteomyelitis with streptavidin and indium-111-labeled biotin. J Nucl Med 1996;37:1655–1662

    CAS  PubMed  Google Scholar 

  37. Lazzeri E, Manca M, Molea N, Marchetti S, Consoli V, Bodei L, Bianchi R, Chinol M, Paganelli G, Mariani G. Clinical validation of the avidin/indium-111 biotin approach for imaging infection/inflammation in orthopaedic patients. Eur J Nucl Med 1999;26:606–614

    Article  CAS  PubMed  Google Scholar 

  38. Attwood PV. The structure and the mechanism of action of pyruvate carboxylase. Int J Biochem Cell Biol 1995;27:231–249

    Article  CAS  PubMed  Google Scholar 

  39. Carragee EJ, Kim D, van der Vlugt T, Vittum D. The clinical use of erythrocyte sedimentation rate in pyogenic vertebral osteomyelitis. Spine 1997;22:2089–2093

    Article  CAS  PubMed  Google Scholar 

  40. Siegel S. Nonparametric statistics for the behavioral sciences. New York: McGraw-Hill, 1956

  41. Aliabadi P, Nikpoor N. Imaging osteomyelitis. Arthritis Rheum 1994;37:617–622

    CAS  PubMed  Google Scholar 

  42. Wagner SC, Schwitzer ME, Morrison WB, Przybylski GJ, Parker L. Can imaging findings help differentiate spinal neuropathic arthropathy from disk space infection? Initial experience. Radiology 2000;214:693–699

    CAS  PubMed  Google Scholar 

  43. Rothman SL. The diagnosis of infections of the spine by modern imaging techniques. Orthop Clin North Am 1996;27:15–31

    CAS  PubMed  Google Scholar 

  44. Samuel A, Paganelli G, Chiesa R, Sudati F, Calvitto M, Melissano G, Grossi A, Fazio F. Detection of prosthetic vascular graft infection using avidin/indium-111-biotin scintigraphy. J Nucl Med 1996;37:55–61

    CAS  PubMed  Google Scholar 

  45. Chinol M, Casalini P, Maggiolo M, Canevari S, Omodeo ES, Caliceti P, Veronese FM, Cremonesi M, Chiolerio F, Nardone E, Siccardi AG, Paganelli G. Biochemical modifications of avidin improve pharmacokinetics and biodistribution, and reduce immunogenicity. Br J Cancer 1998;78:189–197

    CAS  PubMed  Google Scholar 

  46. Caliceti P, Chinol M, Roldo M, Veronese FM, Semenzato A, Salmaso S, Paganelli G. Poly(ethylene glycol)-avidin bioconjugates: suitable candidates for tumor pretargeting. J Control Rel 2002;83:97–108

    Article  CAS  Google Scholar 

  47. Cremonesi M, Ferrari M, Chinol M, Stabin MG, Grana C, Prisco G, Robertson C, Tosi G, Paganelli G. Three-step radioimmunotherapy with 90Y-biotin: dosimetry and pharmacokinetics in cancer patients. Eur J Nucl Med 1999;26:110–120

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Mario Manca

    Present address: Division of Orthopedics, Town Hospital, Massa Carrara, Italy

Authors and Affiliations

  1. Regional Center of Nuclear Medicine, University of Pisa Medical School, Pisa, Italy

    Elena Lazzeri, Paola A. Erba, Duccio Volterrani, Antonio Bottoni & Giuliano Mariani

  2. Division of Nuclear Medicine, University Medical Center Leiden, Leiden, The Netherlands

    Ernest K. J. Pauwels

  3. Division of Orthopedics, University of Pisa Medical School, Pisa, Italy

    Mario Manca & Vincenzo Consoli

  4. Division of Nuclear Medicine, European Institute of Oncology, Milan, Italy

    Lisa Bodei

  5. Division of Radiology, University of Pisa Medical School, Pisa, Italy

    Donatella Trippi

  6. Section of Biostatistics and Epidemiology, CNR Institute of Clinical Physiology and Division of Epidemiology, University of Pisa Medical School, Pisa, Italy

    Renza Cristofani

  7. Division of Nuclear Medicine, Long Island Jewish Medical Center, New York, New York, USA

    Christopher J. Palestro

Authors
  1. Elena Lazzeri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ernest K. J. Pauwels
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paola A. Erba
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Duccio Volterrani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mario Manca
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lisa Bodei
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Donatella Trippi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Antonio Bottoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Renza Cristofani
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Vincenzo Consoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Christopher J. Palestro
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Giuliano Mariani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giuliano Mariani.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lazzeri, E., Pauwels, E.K.J., Erba, P.A. et al. Clinical feasibility of two-step streptavidin/111In-biotin scintigraphy in patients with suspected vertebral osteomyelitis. Eur J Nucl Med Mol Imaging 31, 1505–1511 (2004). https://doi.org/10.1007/s00259-004-1581-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-004-1581-2

Keywords

Search

Navigation