title: Radiation synovectomy using 165Dy ferric-hydroxide and oxidative DNA damage in patients with different types of arthritis.
abstract: Radiation synovectomy is an effective treatment for chronic synovitis refractory to pharmacological treatment in patients with rheumatoid or seronegative arthritis. Concerns persist about possible radiation-induced cytogenetic damage after radiation synovectomy leading to recommendations to use this technique only in the elderly. Micronucleus (MN) frequency in lymphocytes and urinary excretion of 8-hydroxy-2'-deoxyguanosine (8OHdG) as an indicator of cellular oxidative DNA base damage are biomarkers of radiation-induced cytogenetic damage. The course of both biomarkers was studied in patients with different types of chronic synovitis undergoing radiation synovectomy with very short-lived 165Dy-ferric-hydroxide (DFH).
  
  
  METHODS
  Radiation synovectomy of the knee was performed in 13 men and 12 women (mean age, 44+/-15 y) using a mean activity of 9.48+/-1.65 GBq 165Dy-DFH in 27 consecutive treatments. MN frequency in lymphocytes and urinary excretion of 8OHdG, measured by high-performance liquid chromatography, were assessed before and 4 (MN only) and 20 h after radiation synovectomy.
  
  
  RESULTS
  Urinary excretion of 8OHdG in patients (in micromol/mol creatinine; pretreatment mean, 3.1+/-3.4; median, 2.27) was not significantly different from that in healthy volunteers (mean, 2.0+/-1.2; median, 1.87) and not altered by radiation synovectomy (post-treatment mean, 2.5+/-1.5; median, 2.04, NS). An increase in 8OHdG levels after radiation synovectomy of more than 1 SD was found in only 1 patient, who experienced leakage to the lymph nodes but who already had elevated urinary 8OHdG levels before treatment. The frequency of MN/500 binucleated cells (BNCs) was slightly lower in patients (pretreatment mean, 4.3+/-2.6; median, 4.25) than in healthy volunteers (mean, 5.4+/-2.3; median, 5.3) and did not significantly change after therapy, either (4-h post-treatment mean, 3.9+/-2.1, median, 3.8; 20-h post-treatment mean, 4.1+/-2, median 3.8 MN/500 BNC). In 22 of 27 treatments, no leakage to nontarget organs could be monitored, whereas leakage to the local lymph nodes and the liver was detected after 5 treatments.
  
  
  CONCLUSIONS
  Radiation synovectomy using 165Dy-DFH causes no significant radiation burden to most patients as indicated by the absence of adverse changes in levels of biomarkers of cytogenetic damage and a low incidence of leakage. These data suggest that the risk of malignancy may not be elevated.
authors.affiliation: Department of Nuclear Medicine, Occupational Medicine, and Pathology, University of Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Pirich
authors.forename: A
authors.initials: A
authors.lastname: Pilger
authors.forename: E
authors.initials: E
authors.lastname: Schwameis
authors.forename: D
authors.initials: D
authors.lastname: Germadnik
authors.forename: U
authors.initials: U
authors.lastname: Prüfert
authors.forename: E
authors.initials: E
authors.lastname: Havlik
authors.forename: S
authors.initials: S
authors.lastname: Lang
authors.forename: H
authors.initials: H
authors.lastname: Kvaternik
authors.forename: J A
authors.initials: JA
authors.lastname: Flores
authors.forename: P
authors.initials: P
authors.lastname: Angelberger
authors.forename: A
authors.initials: A
authors.lastname: Wanivenhaus
authors.forename: H W
authors.initials: HW
authors.lastname: Rüdiger
authors.forename: H
authors.initials: H
authors.lastname: Sinzinger
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D001168:Arthritis / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D014408:Biomarkers, Tumor / Q000652:urine; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004419:Dysprosium / Q000627:therapeutic use*; D005260:Female; D005290:Ferric Compounds / Q000627:therapeutic use; D006801:Humans; D007136:Immunoglobulins; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000528:radiation effects*; D008297:Male; D011868:Radioisotopes / Q000627:therapeutic use*; D011877:Radionuclide Imaging; D013585:Synovitis / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D013667:Technetium
chemical_list: D014408:Biomarkers, Tumor; D005290:Ferric Compounds; D007136:Immunoglobulins; D011868:Radioisotopes; C065376:technetium Tc 99m immunoglobulin; D004419:Dysprosium; C021024:ferric hydroxide; D013667:Technetium; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine