title: Boron neutron capture synovectomy (BNCS) as a potential therapy for rheumatoid arthritis: radiobiological studies at RA-1 Nuclear Reactor in a model of antigen-induced arthritis in rabbits.
abstract: Rheumatoid arthritis is a chronic autoimmune pathology characterized by the proliferation and inflammation of the synovium. Boron neutron capture synovectomy (BNCS), a binary treatment modality that combines the preferential incorporation of boron carriers to target tissue and neutron irradiation, was proposed to treat the pathological synovium in arthritis. In a previous biodistribution study, we showed the incorporation of therapeutically useful boron concentrations to the pathological synovium in a model of antigen-induced arthritis (AIA) in rabbits, employing two boron compounds approved for their use in humans, i.e., decahydrodecaborate (GB-10) and boronophenylalanine (BPA). The aim of the present study was to perform low-dose BNCS studies at the RA-1 Nuclear Reactor in the same model. Neutron irradiation was performed post intra-articular administration of BPA or GB-10 to deliver 2.4 or 3.9 Gy, respectively, to synovium (BNCS-AIA). AIA and healthy animals (no AIA) were used as controls. The animals were followed clinically for 2 months. At that time, biochemical, magnetic resonance imaging (MRI) and histological studies were performed. BNCS-AIA animals did not show any toxic effects, swelling or pain on palpation. In BNCS-AIA, the post-treatment levels of TNF-α decreased in four of six rabbits and IFN-γ levels decreased in five of six rabbits. In all cases, MRI images of the knee joint in BNCS-AIA resembled those of no AIA, with no necrosis or periarticular effusion. Synovial membranes of BNCS-AIA were histologically similar to no AIA. BPA-BNCS and GB-10-BNCS, even at low doses, would be therapeutically useful for the local treatment of rheumatoid arthritis.
authors: Department of Radiobiology, Comisión Nacional de Energía Atómica (CNEA), Avenida General Paz 1499, B1650KNA, San Martín, Provincia Buenos Aires, Argentina. trivilli@cnea.gov.ar.|Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Argentina. trivilli@cnea.gov.ar.
authors: Verónica A
authors: 0000-0003-3460-3347
authors: VA
authors: Trivillin
authors: LABOATEM (Laboratorio de Biología Osteoarticular, Ingeniería Tisular y Terapias Emergentes), Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina.
authors: Leandro J
authors: LJ
authors: Bruno
authors: LABOATEM (Laboratorio de Biología Osteoarticular, Ingeniería Tisular y Terapias Emergentes), Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina.
authors: David A
authors: DA
authors: Gatti
authors: Cátedra de Diagnóstico por Imágenes, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina.
authors: Mariela
authors: M
authors: Stur
authors: Department of Radiobiology, Comisión Nacional de Energía Atómica (CNEA), Avenida General Paz 1499, B1650KNA, San Martín, Provincia Buenos Aires, Argentina.
authors: Marcela A
authors: MA
authors: Garabalino
authors: Department of Radiobiology, Comisión Nacional de Energía Atómica (CNEA), Avenida General Paz 1499, B1650KNA, San Martín, Provincia Buenos Aires, Argentina.
authors: Andrea Monti
authors: AM
authors: Hughes
authors: Department of Reactors, Comisión Nacional de Energía Atómica (CNEA), Avenida General Paz 1499, B1650KNA, San Martín, Provincia Buenos Aires, Argentina.
authors: Jorge
authors: J
authors: Castillo
authors: Department of Research and Production Reactors, Comisión Nacional de Energía Atómica (CNEA), Presbítero Juan González y Aragon 15, B1802AYA, Ezeiza, Province Buenos Aires, Argentina.
authors: Emiliano C C
authors: EC
authors: Pozzi
authors: Department of Reactors, Comisión Nacional de Energía Atómica (CNEA), Avenida General Paz 1499, B1650KNA, San Martín, Provincia Buenos Aires, Argentina.
authors: Luis
authors: L
authors: Wentzeis
authors: Department of Reactors, Comisión Nacional de Energía Atómica (CNEA), Avenida General Paz 1499, B1650KNA, San Martín, Provincia Buenos Aires, Argentina.
authors: Hugo
authors: H
authors: Scolari
authors: Department of Radiobiology, Comisión Nacional de Energía Atómica (CNEA), Avenida General Paz 1499, B1650KNA, San Martín, Provincia Buenos Aires, Argentina.|Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Argentina.
authors: Amanda E
authors: AE
authors: Schwint
authors: Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Argentina.|LABOATEM (Laboratorio de Biología Osteoarticular, Ingeniería Tisular y Terapias Emergentes), Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina.
authors: Sara
authors: S
authors: Feldman
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced* / Q000532:radiotherapy*; D016754:Boron Neutron Capture Therapy / Q000009:adverse effects / Q000295:instrumentation*; D004195:Disease Models, Animal; D005260:Female; D010047:Ovalbumin / Q000494:pharmacology*; D011817:Rabbits; D011853:Radiobiology; D011879:Radiotherapy Dosage; D012449:Safety; D000074402:Synovectomy; D013583:Synovial Membrane / Q000528:radiation effects
chemical_list: D010047:Ovalbumin
keywords: Antigen-induced arthritis (AIA); Boron neutron capture synovectomy BNCS; Boronophenylalanine (BPA); Decahydrodecaborate (GB-10); RA-1 Nuclear Reactor; Rheumatoid arthritis