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|Title:||Selectively Induced Death of Macrophages in the Synovial Lining of Murine Knee Joints Using 10B-liposomes and Boron Neutron Capture Synovectomy|
|Authors:||VAN LENT Peter; KRIJGER Gerard C.; HOFKENS Wouter; NIEVAART VICTOR ALEXANDER; SLOETJES Annet; MOSS RAYMOND; KONING Gerben A.; VAN DEN BERG Wim|
|Citation:||INTERNATIONAL JOURNAL OF RADIATION BIOLOGY vol. 85 no. 10 p. 860-871|
|Publisher:||TAYLOR & FRANCIS LTD|
|Type:||Articles in periodicals and books|
|Abstract:||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.|
|JRC Directorate:||Energy, Transport and Climate|
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