In Vitro Analysis of Boron - 10 Uptake and Neutron Beam Design for Boron Neutron

Boron Neutron Capture Synovectomy (BNCS) has been proposed as a novel application of the o 1 B(n,a) 7Li reaction for the treatment of Rheumatoid Arthritis (RA). RA is an autoimmune disease of the joints characterized by an inflammation of the synovium, the membrane lining the joint capsule. If drug regimes fail, treatment options are surgical synovectomy or radiation synovectomy. BNCS has advantages over these treatment approaches in that it is non-invasive and does not require the administration of radioactive substances. In BNCS, a o 1 B labelled compound would be injected into the fluid space of the joint where it would be taken up by the synovium. The joint would then be irradiated with neutrons causing intense radiation damage to be delivered to the boron loaded cells. This thesis had two major goals. The first was to conduct an investigation of in vitro uptake of ' 0B by human RA synovium and RA and osteoarthritic cartilage samples, thus allowing an estimate of levels potentially attained in vivo. The primary boron compound investigated was K2B, 2Hz 1 , although some studies were also done with boric acid and boron particulate. Quantification of bulk uptake was performed using Prompt Gamma Neutron Activation Analysis. Cell kill as a result of the boron neutron capture reaction was verified by thermal neutron irradiation of boron-loaded tissue. An attempt was made to determine the spatial distribution of the boron compound using Neutron Induced Alpha Track Autoradiography. The second major aim of this thesis was to design an acceleratorbased neutron beam for BNCS using the Monte Carlo for Neutron and Photon Transport code. A computational model of a knee joint was developed and the therapeutically useful neutron energy range was established by a series of ideal beam studies. A comparison was made between two neutron producing reactions for an accelerator source. Since neutrons coming from an accelerator source are very energetic and thus need moderation to the therapeutically useful neutron energy range, moderator/reflector configurations were examined. Materials for the moderator/reflector assembly were chosen and preliminary configurations were assessed in terms of their potential clinical usefulness in the joint phantom. Thesis Supervisor: Jacquelyn C. Yanch Title: Associate Professor of Nuclear Engineering and Whitaker College of Health Sciences and Technology Thesis Reader: Sonya Shortkroff Title: Research Associate, Harvard Medical School Orthopedic Research Laboratory, Brigham & Women's Hospital