Selectively Induced Death of Macrophages in the Synovial Lining of Murine Knee Joints Using 10B-liposomes and Boron Neutron Capture Synovectomy

Objective: To investigate whether macrophages in the synovial lining can be selectively eliminated by local administration of an improved boron-10 (10B) containing liposome formulation combined with neutron irradiation (boron neutron capture synovectomy [BNCS]). Methods: Disodium dodecahydrododecaborate (Na2 10B12H12) was encapsulated into unilamellar liposomes (10Bliposomes). 10B-liposomes were injected into the mouse knee joint. Amounts of 10B in synovial tissue were measured over time using inductively coupled plasma-optical emission spectrometry (ICP-OES). Arthritis was induced in knee joints of mice. Joint inflammation and cartilage destruction was measured using histology. Results: When a 10 ml 10B-liposome solution (containing 40 mg 10B) was injected into the murine knee joint, high concentrations of 10B were measured in macrophages in the synovial lining (At 24 h 306+226 mg . g71 macrophages). Completing the BNCS by neutron irradiation of the legs 24 h after 10B-liposome injection showed a clear selective depletion of macrophages in synovial lining of the knee joints. An estimated total physical dose of 13+9 Gy was given to the macrophages. When arthritis was induced in the macrophage-depleted joints, swelling of the knee was significantly lower as compared to the controls (53% and 79% lower at days 1 and 3, respectively). Histology confirmed the influx of inflammatory cells was strongly decreased and severe cartilage destruction was almost completely prevented. Conclusion: BNCS using an improved 10B-containing liposome formulation can cause selective depletion of macrophages in the synovial lining of murine knee joints. As a result of this proof-of principle, future applications are recommended.

VAN LENT Peter;  KRIJGER Gerard C.;  HOFKENS Wouter;  NIEVAART Victor Alexander;  SLOETJES Annet;  MOSS Raymond;  KONING Gerben A.;  VAN DEN BERG Wim; 

2009-12-15

TAYLOR & FRANCIS LTD

JRC36945

0955-3002,   

http://www.informaworld.com/smpp/title~content=t713697337,    https://publications.jrc.ec.europa.eu/repository/handle/JRC36945,   

10.3109/09553000903072454,