Boron neutron capture synovectomy: Treatment of rheumatoid arthritis basedon the B-10(n,alpha)Li-7 nuclear reaction

A novel application of the B-10(n,alpha)Li-7 nuclear reaction for the treat ment of rheumatoid arthritis is under investigation. Rheumatoid arthritis i s characterized by a painful inflammation of the membrane (synovium) lining articular joints. Since the tissue targeted for treatment is the diseased synovial membrane and the goal is synovial ablation ("synovectomy"), the pr oposed treatment is called Boron Neutron Capture Synovectomy. Development o f this therapeutic modality has been carried out in a number of areas, incl uding the ex vivo and in vivo evaluation of B-10 in arthritic synovium, and the design and construction of a dedicated neutron beam assembly for joint irradiation. Ex vivo evaluation of boron uptake in human arthritic synoviu m using K2B12H12 has demonstrated that B-10 concentrations of 550-2400 ppm are repeatedly obtained. Preliminary in vivo experiments in an arthritic ra bbit model have shown that synovial boron concentrations of approximately 2 65-950 ppm are obtained at 15 min past intra-articular injection. With thes e uptake levels experimental evaluation of the efficacy of BNCS in the trea tment of rheumatoid arthritis in an animal model can be carried out. Optima l neutron beams suitable for joint irradiation are shown to be lower in ene rgy than those used for BNCT. An assembly comprising a graphite reflector s urrounding a D2O moderator has been designed, constructed, and installed on the 4.1 MeV tandem electrostatic accelerator at MIT's Laboratory for Accel erator Beam Applications. Monte Carlo calculations predict a total therapy time of between 8.4 and 31 min for the human knee, depending on the charged particle reaction used; a particle beam current of 1 mA is assumed. Therap y times to treat a human finger joint range from 4 to 14 min for a 1 mA acc elerator current. These treatment times are based on average B-10 in vivo u ptake levels (observed experimentally in the rabbit knee) of 950 ppm and a 10000 RBE-cGy treatment dose. It is concluded that Boron Neutron Capture Sy novectomy, consisting of intra-articular injection of a B-10-labeled compou nd followed by neutron irradiation of the joint, has considerable potential as a means of treating rheumatoid arthritis. (C) 1999 American Association of Physicists in Medicine. [S0094-2405(99)01103-7].