Boron neutron capture synovectomy: Treatment of rheumatoid arthritis based on the nuclear reaction

Abstract

A novel application of the nuclear reaction for the treatment of rheumatoid arthritis is under investigation. Rheumatoid arthritis is 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 proposed treatment is called Boron Neutron Capture Synovectomy. Development of this therapeutic modality has been carried out in a number of areas, including the ex vivo and in vivo evaluation of 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 synovium using has demonstrated that concentrations of 550–2400 ppm are repeatedly obtained. Preliminary in vivo experiments in an arthritic rabbit model have shown that synovial boron concentrations of approximately 265–950 ppm are obtained at 15 min post intra‐articular injection. With these uptake levels experimental evaluation of the efficacy of BNCS in the treatment of rheumatoid arthritis in an animal model can be carried out. Optimal neutron beams suitable for joint irradiation are shown to be lower in energy than those used for BNCT. An assembly comprising a graphite reflector surrounding a moderator has been designed, constructed, and installed on the 4.1 MeV tandem electrostatic accelerator at MIT's Laboratory for Accelerator 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. Therapy times to treat a human finger joint range from 4 to 14 min for a 1 mA accelerator current. These treatment times are based on average in vivo uptake levels (observed experimentally in the rabbit knee) of 950 ppm and a 10 000 RBE‐cGy treatment dose. It is concluded that Boron Neutron Capture Synovectomy, consisting of intra‐articular injection of a ‐labeled compound followed by neutron irradiation of the joint, has considerable potential as a means of treating rheumatoid arthritis.