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Nuklearmedizin 2012; 51(01): 17-25
DOI: 10.3413/nukmed-0423-11-08
Original article
Schattauer GmbH

Biological dosimetry after radio - synoviorthesis with rhenium-186 sulphide and erbium-169 citrate

Biologische Dosimetrie nach Radiosynoviorthese mit Rhenium-186-sulfid und Erbium-169-zitrat
R. Klett
1   Nuclear medicine practice, Gießen, Germany
2   Faculty of Medicine, Justus-Liebig-University Gießen, Germany
,
A. Schnurbus-Duhs
2   Faculty of Medicine, Justus-Liebig-University Gießen, Germany
,
G. Mödder
3   Nuclear medicine practice, Köln, Germany
,
E. Schmid
4   Institute for Cell Biology, Center for Integrated Protein Science Munich, University of Munich, Germany
,
M. Voth
5   Ruppiner Kliniken GmbH, Neuruppin, Germany
› Author Affiliations
Further Information

Publication History

received: 14 August 2011

accepted in revised form: 05 September 2011

Publication Date:
29 December 2017 (online)

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Summary

Radiosynoviorthesis (RSO) with the nuclides rhenium-186 sulphide (186Re) and erbium-169 citrate (169Er) is an established concept for the treatment of persistent synovitis of medium and small sized joints. The aim of the present studies was to investigate the biological radiation effect based on analysing chromosome aberrations. Patients, methods: Immediately before and 17 to 19 days (186Re) or 45 to 50 (169Er) days after RSO with 186Re or 169Er colloid and subsequent immobilisation of the treated joint, blood samples of a total of 23 patients were collected. The yield of dicentric chromosomes in lymphocytes was determined exclusively in metaphases of the first cell cycle in vitro. In addition, for 186Re the activity leakage was measured three days after RSO by whole-body scintigraphy. Results: No statistically significant increase in the number of dicentric chromosomes (40 and 88 before and 59 and 105 after treatment with 186Re and 169Er, respectively) in a total of 47 017 cells analysed from 46 blood samples could be found as a result of RSO. For 186Re an activity leakage of 3.9% ± 7% with a maximum of 23.4% corresponding to an effective dose of 2.8 ± 4.5 mSv , respectively 13.8 mSv, was determined. Also in the case of the maximum leakage no significant increase of dicentric chromosomes were detected. Conclusions: No significant biological radiation effect can be detected after RSO with 186Re and 169Er, also in cases of high leakage. Therefore, RSO can be classified as a save therapeutic procedure without a relevant radiation risk.

Zusammenfassung

Ziel: Die Radiosynoviorthese mit den Nukliden Rhenium-186-sulfid (186Re) und Erbium-169-zitrat (169Er) ist etabliert als Verfahren zur lokalen Therapie entzündlich-rheumatischer Erkrankungen mittelgroßer und kleiner Gelenke. Anhand der Auswertung von Chromosomenaberrationen soll die biologische Strahlenwirkung der Therapie untersucht werden. Patienten, Methoden: Direkt vor und 17 bis 19 Tage (186Re) bzw. 45 bis 50 Tage (169Er) nach RSO mit 186Re und 169Er sowie anschließender Ruhigstellung des behandelten Gelenks für 48 Stunden wurden bei 23 Patienten Blutproben entnommen. Die Häufigkeit dizentrischer Chromosomen in Lymphozyten in der Metaphase wurde nach der ersten Zellteilung in vitro bestimmt. Ergänzend wurde für 186Re drei Tage nach RSO der Aktivitätsabtransport mittels Ganzkörperszintigraphie ermittelt. Ergebnisse: In den insgesamt 47 017 analysierten Zellen der 46 Blutproben wurde keine signifikante Zunahme der dizentrischen Chromosomen durch die RSO (40 bzw. 88 vor und 59 bzw. 105 nach der RSO mit 186Re bzw. 169Er) beobachtet. Bei der RSO mit 186Re ergab sich ein Aktivitätsabtransport von 3,9% ± 7% entsprechend einer effektiven Dosis von 2,8 ± 4,5 mSv. Auch beim maximalen Abtransport von 23,4% (13,8 mSv) fand sich keine Zunahme der dizentrischen Chromosomen. Schluss - folgerung: Bei der RSO mit 186Re und 169Er findet sich, auch im Falle eines deutlichen Aktivitätsabtransportes, kein signifikanter biologischer Strahleneffekt. Insofern kann die RSO als sichere Therapie ohne relevantes Strahlenrisiko eingestuft werden.

Keywords

Rhenium-186 - erbium-169 - radiosynoviorthesis - chromosome aberration - biological dosimetry - activity leakage

Schlüsselwörter

Rhenium-186 - Erbium-169 - Radiosynoviorthese - Chromosomenaberrationen - biologische Dosimetrie - Aktivitätsabtransport
 

  • References

  • 1 Awa AA, Neel JV. Cytogenetic ‘rogue’ cells: what is their frequency, origin, and evolutionary Significance?. Proc Natl Acad Sci USA 1986; 83: 1021-1025.
    CrossrefPubMedSearch in Google Scholar
  • 2 Bauchinger M. Cytogenetic research after accidental radiation exposure. Stem Cells 1995; 13 (Suppl. 01) 182-190.
    Search in Google Scholar
  • 3 Dikomey E. Determination of DNA damage in vitro. Nuklearmedizin 2010; 49 (Suppl. 01) S64-S68.
    Thieme ConnectPubMedSearch in Google Scholar
  • 4 Edwards AA. The use of chromosomal aberrations in human lymphocytes for biological dosimetry. Radiat Res 1997; 148 (Suppl. 05) S39-S44.
    CrossrefPubMedSearch in Google Scholar
  • 5 Falcon de Vargas V, Fernandez-Palazzi F. Cytogenetic studies in patients with hemophilic hemarthrosis treated by 198Au, 186Re, and 90Y radioactive synoviorthesis. J Pediatr Orthop B 2000; 9: 52-54.
    CrossrefPubMedSearch in Google Scholar
  • 6 Farahati J, Schulz G, Wendler J. et al. Multivariate analysis of factors influencing the effect of radiosynovectomy. Nuklearmedizin 2002; 41: 114-119.
    Thieme ConnectPubMedSearch in Google Scholar
  • 7 Fischer M, Mödder G. Radionuclide therapy of inflammatory joint diseases. Nucl Med Commun 2002; 23: 829-831.
    CrossrefPubMedSearch in Google Scholar
  • 8 Göbel D, Gratz S, von Rothkirch T. et al. Radiosynoviorthesis with rhenium-186 in rheumatoid arthritis: a prospective study of three treatment regimens. Rheumatol Int 1997; 17: 105-108.
    CrossrefPubMedSearch in Google Scholar
  • 9 Grmek M, Milcinski M, Fettich J. et al. Radiation exposure of hemophiliacs after radiosynoviorthesis with 186Re colloid. Cancer Biother Radiopharm 2007; 22: 417-422.
    CrossrefPubMedSearch in Google Scholar
  • 10 Gumpel JM, Stevenson AC. Chromosomal damage after intra-articular injection of different colloids of yttrium 90. Rheumatol Rehabil 1975; 14: 7-12.
    CrossrefPubMedSearch in Google Scholar
  • 11 Hänscheid A, Lassmann M, Pinkert J. et al. Strahlenexposition des Patienten nach Radiosynoviorthese mit Er-169 und Re-186. Nuklearmedizin 2005; 44: A136.
    Search in Google Scholar
  • 12 Houvenagel E, Debouvry L, Leloire O. et al. Cytogenetic anomalies after isotope synoviorthesis in rheumatoid polyarthritis. Rev Rhum Mal Osteoartic 1991; 58: 31-34.
    PubMedSearch in Google Scholar
  • 13 ICRP. Relative biological effectiveness (RBE), quality factor (Q), and radiation weighting factor (wR). Annals of the International Commission on Radiation Protection, Publication 92.. New York: Elsevier; 2003
    Search in Google Scholar
  • 14 International Atomic Energy Agency (IAEA). Biological dosimetry: Chromosomal aberration analysis for dose assessment. Technical Reports. 1986 Series No. 260 1-68.
    PubMedSearch in Google Scholar
  • 15 Jahangier ZN, Moolenburgh JD, Jacobs JW. et al. The effect of radiation synovectomy in patients with persistent arthritis: a prospective study. Clin Exp Rheumatol 2001; 19: 417-424.
    PubMedSearch in Google Scholar
  • 16 Joksic G, Petrovic S, Ilic Z. Age-related changes in radiation-induced micronuclei among healthy adults. Braz J Med Biol Res 2004; 37: 1111-1117.
    CrossrefPubMedSearch in Google Scholar
  • 17 Kanda R, Jiang T, Hayata I, Kobayashi S. Effects of Colcemid concentration on chromosome aberration analysis in human lymphocytes. J Radiat Res (Tokyo) 1994; 35: 41-47.
    CrossrefPubMedSearch in Google Scholar
  • 18 Klett R, Puille M, Matter HP. et al. Activity leakage and radiation exposure in radiation synovectomy of the knee: influence of different therapeutic modalities. Z Rheumatol 1999; 58: 207-212.
    CrossrefPubMedSearch in Google Scholar
  • 19 Kresnik E, Mikosch P, Gallowitsch HJ. et al. Clinical outcome of radiosynoviorthesis: a meta-analysis including 2190 treated joints. Nucl Med Commun 2002; 23: 683-688.
    CrossrefPubMedSearch in Google Scholar
  • 20 Kretschko J, Wellner J. Dosimetrie und Strahlenschutz. Büll U, Schicha H, Biersack H-J. et al. Nuklearmedizin.. Stuttgart: Thieme; 1994: 139-156.
    Search in Google Scholar
  • 21 Krogh Jensen M, Nyfors A. Cytogenetic effect of methotrexate on human cells in vivo: Comparison between results obtained by chromosome studies on bone-marrow cells and blood lymphocytes and by the micronucleus test. Mutat Res 1979; 64: 339-343.
    CrossrefPubMedSearch in Google Scholar
  • 22 Lacki JK, Schochat T, Sobieska M. et al. Immunological studies in patients with rheumatoid arthritis treated with methotrexate or cyclophosphamide. Z Rheumatol 1994; 53: 76-82.
    PubMedSearch in Google Scholar
  • 23 Leonard A, Rueff J, Gerber GB. et al. Usefulness and limits of biological dosimetry based on cytogenetic methods. Radiat Prot Dosim 2005; 115: 448-454.
    CrossrefPubMedSearch in Google Scholar
  • 24 Manil L, Voisin P, Aubert B. et al. Physical and biological dosimetry in patients undergoing radiosynoviorthesis with erbium-169 and rhenium-186. Nuclear Med Comm 2001; 22: 405-416.
    Search in Google Scholar
  • 25 Menkes CJ. Is there a place for chemical and radiation synovectomy in rheumatic diseases?. Rheumatol Rehabil 1979; 18: 65-77.
    CrossrefPubMedSearch in Google Scholar
  • 26 Mondello C, Giorgi R, Nuzzo F. Chromosomal effects of methotrexate on cultured human lymphocytes. Mutat Res 1984; 139: 67-70.
    CrossrefPubMedSearch in Google Scholar
  • 27 Mustonen R, Lindholm C, Tawn EJ. et al. The incidence of cytogenetically abnormal rogue cells in peripheral blood. Int J Radiat Biol 1998; 74: 781-785.
    CrossrefPubMedSearch in Google Scholar
  • 28 Neel JV, Major EO, Awa AA. et al. Hypothesis: „Rogue cell“-type chromosomal damage in lymphocytes is associated with infection with the JC human polyoma virus and has implications for oncopenesis. Proc Natl Acad Sci USA 1996; 93: 2690-2695.
    CrossrefPubMedSearch in Google Scholar
  • 29 Runge R, Wendisch M, Wunderlich G. et al. DNA damage in lymphocytes after irradiation with 211At and 188Re. Quantification by alkaline and neutral comet assay. Nukleamedizin 2009; 48: 221-226.
    Search in Google Scholar
  • 30 Ruotsi A, Hypén M, Rekonen A. et al. Erbium-169 versus triamcinolone hexacetonide in the treatment of rheumatoid finger joints. Ann Rheum Dis 1979; 38: 45-47.
    CrossrefPubMedSearch in Google Scholar
  • 31 Schlaghecke R, Beuscher D, Kornely E. et al. Effects of glucocorticoids in rheumatoid arthritis. Diminished glucocorticoid receptors do not result in gluocorticoid resistance. Arthritis Rheum 1994; 37: 1127-1131.
    CrossrefPubMedSearch in Google Scholar
  • 32 Schmid E, Schlegel D, Guldbakke S. et al. RBE of nearly monoenergetic neutrons at energies of 36 keV -14.6 MeV for induction of dicentrics in human lymphocytes. Radiat Environ Biophys 2003; 42: 87-94.
    CrossrefPubMedSearch in Google Scholar
  • 33 Schmid E, Selbach HJ, Voth M. et al. The effect of the β-emitting yttrium-90 citrate on the dose response of dicentric chromosomes in human lymphocytes: a basis for biological dosimetry after radiosynoviorthesis. Radiat Environ Biophys 2006; 45: 93-98.
    CrossrefPubMedSearch in Google Scholar
  • 34 Shmakova NL, Nasonova EA, Krasavin EA. et al. Induction of chromosome aberrations and micronuclei in human peripheral blood lymphocytes at low dose of radiation. Radiats Biol Radioecol 2006; 46: 480-487.
    PubMedSearch in Google Scholar
  • 35 Stephan G, Pressl S. Chromosomal aberrations in peripheral lymphocytes from healthy subjects as detected in first cell division. Mutat Res 1999; 446: 231-237.
    CrossrefPubMedSearch in Google Scholar
  • 36 Stephan G, Schneider K, Panzer W. et al. Enhanced yield of chromosome aberrations after CT examinations in paediatric patients. Int J Radiat Biol 2007; 83: 1-7.
    CrossrefPubMedSearch in Google Scholar
  • 37 Van den Brink HR, van Wijk MJ, Bijlsma JW. Influence of steroid hormones on proliferation of peripheral blood mononuclear cells in patients with rheumatoid arthritis. Br J Haematol 1992; 31: 663-667.
    Search in Google Scholar
  • 38 Venkatachalam P, Paul SFD, Mohankumar MN. et al. Higher frequency of dicentrics and micronuclei in peripheral blood lymphocytes of cancer patients. Mutat Res 1999; 425: 1-8.
    CrossrefPubMedSearch in Google Scholar
  • 39 Voth M, Klett R, Lengsfeld P. et al. Biological dosimetry after yttrium-90 citrate colloid radiosynoviorthesis. Nuklearmedizin 2006; 45: 223-228.
    Thieme ConnectPubMedSearch in Google Scholar
  • 40 Weetman AP. Radioiodine treatment for benign thyroid diseases. Clin Endocrinol 2007; 66: 757-764.
    CrossrefPubMedSearch in Google Scholar