[Dy-166]Dy/Ho-166 hydroxide macro aggregates: an in vivo generator system for radiation synovectomy

摘要

Radiation synovectomy is an effective treatment in patients suffering from inflammatory-rheumatoid and degenerative joint diseases. The aim of this work was to examine the feasibility of preparing dysprosium-166 (Dy-166)/holmium-166(Ho-166) hydroxide macroaggregates ([Dy-166]Dy/Ho-166-HM) as an in vivo generator for radiation synovectomy evaluating whether the stability of Dy-166-HM and Ho-166-HM complexes is maintained when the daughter Ho-166 is formed. The Monte Carlo (MCNP4B) theoretical depth dose profile for the in vivo [Dy-166]Dy/Ho-166 generator system in a joint model was calculated and compared with that produced by Y-90, Sm-153 and Ho-166. Dy-166 was obtained by neutron irradiation of enriched (Dy2O3)-Dy-164 in a Triga Mark III reactor. Macroaggregates were prepared by reaction of [Dy-166]DyCl3 with 0.5 M NaOH in an ultrasonic bath. [Dy-166]Dy/Ho-166-HM was obtained with radiochemical purity > 99.5% and with the majority of particles in the 2-5 pm range. In vitro studies demonstrated that the radio-macroaggregates are stable in saline solution and human serum without a significant change in the particle size over 14d, suggesting that no translocation of the daughter nucleus occurs subsequent to beta(-) decay of Dy-166. Biological studies in normal rats demonstrated high retention in the knee joint even 7 d after [Dy-166]Dy/Ho-166-HM administration. The Monte Carlo (MCNP4B) theoretical depth dose profiles in a joint model, showed that the in vivo [Dy-166]Dy/(HO)-H-166 generator system would produce 25% and 50% less radiation dose to the articular cartilage and bone surface, respectively, than that produced by Y-90 or pure Ho-166 in a treatment with the same therapeutic dose to the synovium surface. Despite that Sm-153 showed the best depth dose profile sparing doses to healthy tissues, the use of Dy-166 could provide the advantage of being applied in patients that cannot be reached within a few hours from a nuclear reactor and to produce less radiation exposure to the medical personnel during the radiopharmaceutical administration. (C) 2004 Elsevier Ltd. All rights reserved.