Radiation synovectomy using Dy-165 ferric-hydroxide and oxidative DNA damage in patients with different types of arthritis

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 Dy-165-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 Dy-165-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 mu mol/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. Conclusion: Radiation synovectomy using Dy-165-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.