^99mTc-labeled ubiquicidin scintigraphy

Summary

Aim: Hip prosthesis implantation has witnessed a significant increase in recent years. Despite the advantages of this surgical procedure, it has some complications, the most serious of which is prosthetic infection. This study was conducted to investigate the feasibility of ^99mTc-UBI scintigraphy in detection of infectious foci in painful hip prosthesis. UBI (Ubiquicidin 29–41) is an antimicrobial peptide fragment with the ability to target the bacterial colony directly. Patients, methods: 34 patients, aged 20–79 years, with painful hip prosthesis were included. ^99mTc-UBI scan and three phase bone scan were performed and two nuclear medicine specialists interpreted the UBI scans with and without bone scan results at hand. Both qualitative and semiquantitative methods were used to interpret the 30 minute post injection images. The patients were actively followed up. According to the surgical findings, microbiological culture and active follow up, final diagnosis was made. Results: 24 negative and 10 positive UBI scans were recorded. The sensitivity, specificity, negative and positive predictive values and accuracy of the study were all 100%. Bone scan did not have any influence on UBI interpretation. We were able to achieve excellent differentiation between infected and non-infected prostheses with a cut off value of 1.8 for target to non target (T/NT) ratio. No adverse effects were noticed following UBI scan. Conclusion: Based on the findings, the authors believe that ^99mTc-UBI scintigraphy, with its high sensitivity and specificity, provides the physician with an excellent tool for differentiating infection from aseptic loosening of hip prostheses. Using this radiopharmaceutical, it is possible to obtain highly accurate results only 30 minutes after the beginning of the study.

Zusammenfassung

Ziel: In den vergangenen Jahren verzeichnete die Implantation von Hüftgelenksprothesen eine deutliche Zunahme. Trotz seiner Vorteile weist dieses chirurgische Verfahren einige Komplikationen auf, von denen die Protheseninfektion am schwerwiegendsten ist. In dieser Studie sollte geprüft werden, ob sich die ^99mTc- UBI-Szintigraphie dazu eignet, Infektionsherde in schmerzhaften Hüftprothesen zu erkennen. UBI (Ubiquicidin 29–41) ist ein Fragment eines antimikrobiellen Peptids, mit dem sich Bakterienkolonien direkt darstellen lassen. Patienten, Methoden: 34 Patienten (Alter 20–79 Jahre) mit schmerzhaften Hüftprothesen wurden untersucht. Es wurden eine ^99mTc- UBI-Aufnahme und ein 3-Phasen-Skelettszintigramm angefertigt; zwei Spezialisten für Nuklearmedizin begutachteten die UBI-Aufnahmen, mit oder ohne Vergleich mit den Skelettszintigrammen. Für die Interpretation der Aufnahmen 30 Minuten nach der Injektion wurden sowohl qualitative als auch semiquantitative Methoden angewendet. Die Patienten wurden nachbeobachtet. Die endgültige Diagnose wurde anhand der chirurgischen Befunde, mikrobiologischen Kulturen und des aktiven Follow-ups gestellt. Ergebnisse: Es ergaben sich 24 negative und 10 positive UBI-Aufnahmen. Sensitivität, Spezifität, negativer und positiver Vorhersagewert und Treffsicherheit der Studie lagen alle bei 100%. Das Skelettszintigramm hatte keinerlei Einfluss auf die UBI-Interpretation. Außerdem konnten wir ausgezeichnet zwischen infizierten und nicht infizierten Prothesen differenzieren, wobei der Cut-off-Wert bei 1,8 lag. Nach der UBI-Aufnahme wurden keine unerwünschten Wirkungen festgestellt. Schlussfolgerung: Auf der Basis dieser Ergebnisse glauben die Autoren, dass die ^99mTc-UBI-Szintigraphie mit ihrer hohen Sensitivität und Spezifität eine exzellente Methode ist, um infektiöse von aseptischen Lockerungen der Hüftprothesen abzugrenzen. Dieses Radiopharmakon ermöglicht es, in nur 30 Minuten nach Beginn der Untersuchung äußerst genaue Ergebnisse zu erzielen.

Keywords

Hip prosthesis - prosthesis infection - arthroplasty - ubiquicidin - UBI

Schlüsselwörter

Hüftprothese - Protheseninfektion - Arthro plastie - Ubiquicidin - UBI

• References

• 1 Akhtar MS, Khan ME, Khan B. et al. An imaging analysis of ^99mTc-UBI (29-41) uptake in S. aureus infected thighs of rabbits on ciprofloxacin treatment. Eur J Nucl Med Mol Imaging 2008; 35: 1056-1064.
• 2 Akhtar MS, Qaisar A, Irfanullah J. et al. Antimicrobial peptide ^99mTc-ubiquicidin 29–41 as human infection-imaging agent: clinical trial. J Nucl Med 2005; 46: 567-573.
• 3 Bauer TW, Parvizi J, Kobayashi N. et al. Diagnosis of periprosthetic infection. J Bone Joint Surg Am 2006; 88: 869-882.
• 4 Boubaker A, Delaloye AB, Blanc CH. et al. Immunoscintigraphy with antigranulocyte monoclonal antibodies for the diagnosis of septic loosening of hip prostheses. Eur J Nucl Med 1995; 22: 139-147.
• 5 Britton KE, Wareham DW, Das SS. et al. Imaging bacterial infection with ^99mTc-ciprofloxacin (Infecton). J Clin Pathol 2002; 55: 817-823.
• 6 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: 442-450.
• 7 Chryssikos T, Parvizi J, Ghanem E. et al. FDG-PET imaging can diagnose periprosthetic infection of the hip. Clin Orthop Relat Res 2008; 466: 1338-1342.
• 8 Das SS, Britton KE, Solanki KK. et al. ^99mTc-ciprofloxacin scintigraphy in rabbit model of prosthetic joint infection. J Nucl Med 2003; 44: 317-320.
• 9 Delank KS, Schmidt M, Michael JW. et al. 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.
• 10 Gandomkar M, Najafi R, Shafiei M. et al. Clinical evaluation of antimicrobial peptide [^99mTc/Tricine/HYNIC(0)]ubiquicidin 29–41 as a human-specific infection imaging agent. Nucl Med Biol 2009; 36: 199-205.
• 11 Garcia-Barrecheguren E, Rodriguez Fraile M, Toledo Santana G. et al. FDG-PET: a new diagnostic approach in hip prosthetic replacement. Rev Esp Med Nucl 2007; 26: 208-220.
• 12 Jimenez Heffernan A, Contreras Puertas PI, Rebollo Aguirre AC. ^99mTc-labelled antigranulocyte anibody fragment Fab scintigraphy (sulesomab, leukoscan) and three-phase bone scintigraphy in the study of painful hip and knee prosthesis. Rev Esp Med Nucl 2002; 21: 286-293.
• 13 Kaltsas DS. Infection after total hip arthroplasty. Ann R Coll Surg Engl 2004; 86: 267-271.
• 14 Klett R, Steiner D, Puille M. et al. Antigranulocyte scintigraphy of septic loosening of hip endoprosthesis: effect of different methods of analysis. Nuklearmedizin 2001; 40: 75-79.
• 15 Kordelle J, Klett R, Stahl U. et al. Stage diagnostics for postinfection revision of hip and knee replacement: value of laboratory parameters and antigranulocyte scintigraphy. Z Orthop Ihre Grenzgeb 2003; 141: 547-553.
• 16 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: 2122-2132.
• 17 Lorberboym M, Feldbrin Z, Hendel D. et al. 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: 534-537.
• 18 Love C, Marwin SE, Palestro CJ. Nuclear medicine and the infected joint replacement. Semin Nucl Med 2009; 39: 66-78.
• 19 Love C, Marwin SE, Tomas MB. 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: 1864-1871.
• 20 Love C, Tomas MB, Marwin SE. et al. Role of nuclear medicine in diagnosis of the infected joint replacement. Radiographics 2001; 21: 1229-1238.
• 21 Mayer-Wagner S, Mayer W, Maegerlein S. et al. Use of ¹⁸F-FDG-PET in the diagnosis of endoprosthetic loosening of knee and hip implants. Arch Orthop Trauma Surg 2010; 130: 1231-1238.
• 22 Melendez-Alafort L, Nadali A, Pasut G. et al. Detection of sites of infection in mice using ^99mTc-labeled PN(2)S-PEG conjugated to UBI and ^99mTc-UBI: a comparative biodistribution study. Nucl Med Biol 2009; 36: 57-64.
• 23 Melendez-Alafort L, Rodriguez-Cortes J, Ferro-Flores G. et al. Biokinetics of ^99mTc-UBI 29–41 in humans. Nucl Med Biol 2004; 31: 373-379.
• 24 Morguet AJ, Munz DL, Ivancevic V. et al. The clinical importance of scintigraphy with the murine monoclonal antigranulocyte antibody BW 250/183 for the diagnosis of prosthesis-related endocarditis. Dtsch Med Wochenschr 1995; 120: 861-866.
• 25 Nibbering PH, Welling MM, Paulusma-Annema A. et al. ^99mTc-labeled UBI 29–41 peptide for monitoring the efficacy of antibacterial agents in mice infected with Staphylococcus aureus. J Nucl Med 2004; 45: 321-326.
• 26 Pakos EE, Trikalinos TA, Fotopoulos AD. et al. Prosthesis infection: diagnosis after total joint arthroplasty with antigranulocyte scintigraphy with ^99mTc-labeled monoclonal antibodies--a metaanalysis. Radiology 2007; 242: 101-108.
• 27 Palestro CJ. Nuclear medicine, the painful prosthetic joint, and orthopedic infection. J Nucl Med 2003; 44: 927-929.
• 28 Palestro CJ, Kim CK, Swyer AJ. et al. Total-hip arthroplasty: periprosthetic indium-111-labeled leukocyte activity and complementary technetium-⁹⁹m-sulfur colloid imaging in suspected infection. J Nucl Med 1990; 31: 1950-1955.
• 29 Pelosi E, Baiocco C, Pennone M. 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: 438-444.
• 30 Reinartz P, Mumme T, Hermanns B. et al. Radionuclide imaging of the painful hip arthroplasty: positron-emission tomography versus triple-phase bone scanning. J Bone Joint Surg Br 2005; 87: 465-470.
• 31 Sepulveda-Mendez J, de Murphy CA, Rojas-Bautista JC. et al. Specificity of ^99mTc-UBI for detecting infection foci in patients with fever in study. Nucl Med Commun 2010; 31: 889-895.
• 32 Sonmezoglu K, Sonmezoglu M, Halac M. 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: 567-574.
• 33 Vallejo E, Martinez I, Tejero A. et al. Clinical utility of ^99mTc-labeled ubiquicidin 29–41 antimicrobial peptide for the scintigraphic detection of mediastinitis after cardiac surgery. Arch Med Res 2008; 39: 768-774.
• 34 Van der Bruggen W, Bleeker-Rovers CP, Boerman OC. et al. PET and SPECT in osteomyelitis and prosthetic bone and joint infections: a systematic review. Semin Nucl Med 2010; 40: 3-15.
• 35 Welling MM, Visentin R, Feitsma HI. et al. Infection detection in mice using ^99mTc-labeled HYNIC and N2S2 chelate conjugated to the antimicrobial peptide UBI 29–41. Nucl Med Biol 2004; 31: 503-509.
• 36 Zhuang H, Chacko TK, Hickeson M. et al. Persistent non-specific FDG uptake on PET imaging following hip arthroplasty. Eur J Nucl Med Mol Imaging 2002; 29: 1328-1333.
• 37 Zoccali C, Teori G, Salducca N. The role of FDG-PET in distinguishing between septic and aseptic loosening in hip prosthesis: a review of literature. Int Orthop 2009; 33: 1-5.