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 ((10)B) containing liposome formulation combined with neutron irradiation (boron neutron capture synovectomy [BNCS]).


METHODS
Disodium dodecahydrododecaborate (Na(2)(10)B(12)H(12)) was encapsulated into unilamellar liposomes ((10)B-liposomes). (10)B-liposomes were injected into the mouse knee joint. Amounts of (10)B 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 microl (10)B-liposome solution (containing 40 microg (10)B) was injected into the murine knee joint, high concentrations of (10)B were measured in macrophages in the synovial lining (At 24 h 306+/-226 microg. g(-1) macrophages). Completing the BNCS by neutron irradiation of the legs 24 h after (10)B-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.


CONCLUSIONS
BNCS using an improved (10)B-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 L E M
PL
Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. P.vanlent@reuma.umcn.nl
Krijger
Gerard C
GC
Hofkens
Wouter
W
Nievaart
Victor A
VA
Sloetjes
Annet W
AW
Moss
Ray L
RL
Koning
Gerben A
GA
van den Berg
Wim B
WB
D000818:Animals; D001169:Arthritis, Experimental / Q000473:pathology* / Q000532:radiotherapy*; D001895:Boron / Q000008:administration & dosage; D016754:Boron Neutron Capture Therapy; D016923:Cell Death / Q000528:radiation effects; D007270:Injections, Intra-Articular; D007554:Isotopes / Q000008:administration & dosage; D007596:Joints / Q000473:pathology / Q000528:radiation effects; D008081:Liposomes; D008264:Macrophages / Q000473:pathology* / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D011879:Radiotherapy Dosage; D013583:Synovial Membrane / Q000473:pathology* / Q000528:radiation effects*
D007554:Isotopes; D008081:Liposomes; D001895:Boron