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
Autor: | Hugo Scolari, Verónica A. Trivillin, David A. Gatti, Sara Feldman, Luis Wentzeis, Amanda E. Schwint, Jorge Castillo, Emiliano C. C. Pozzi, Marcela A. Garabalino, Leandro J. Bruno, Mariela Stur, Andrea Monti Hughes |
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Rok vydání: | 2016 |
Předmět: |
musculoskeletal diseases
Biodistribution Pathology medicine.medical_specialty Necrosis Ra-1 Nuclear Reactor CIENCIAS MÉDICAS Y DE LA SALUD Ovalbumin medicine.medical_treatment Biophysics Arthritis Ciencias de la Salud Inflammation Synovectomy Rheumatoid Arthritis Boron Neutron Capture Therapy Boron Neutron Capture Synovectomy Bncs 030218 nuclear medicine & medical imaging Arthritis Rheumatoid 03 medical and health sciences 0302 clinical medicine medicine Animals Decahydrodecaborate (Gb-10) General Environmental Science Radiation medicine.diagnostic_test Antigen-Induced Arthritis (Aia) business.industry Synovial Membrane Radiobiology Magnetic resonance imaging Radiotherapy Dosage medicine.disease Otras Ciencias de la Salud Disease Models Animal Effusion 030220 oncology & carcinogenesis Rheumatoid arthritis Female Rabbits medicine.symptom Boronophenylalanine (Bpa) Safety Nuclear medicine business |
Zdroj: | Radiation and environmental biophysics. 55(4) |
ISSN: | 1432-2099 |
Popis: | 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. Fil: Trivillin, Verónica Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina Fil: Bruno, Leandro J.. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina Fil: Gatti, Claudio David. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina Fil: Stur, Mariela. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina Fil: Garabalino, Marcela Alejandra. Comisión Nacional de Energía Atómica; Argentina Fil: Monti Hughes, Andrea. Comisión Nacional de Energía Atómica; Argentina Fil: Castillo, Jorge Alberto. Comisión Nacional de Energía Atómica; Argentina Fil: Pozzi, Emiliano César Cayetano. Comisión Nacional de Energía Atómica; Argentina Fil: Wentzeis, Luis. Comisión Nacional de Energía Atómica; Argentina Fil: Scolari, Hugo. Comisión Nacional de Energía Atómica; Argentina Fil: Schwint, Amanda Elena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina Fil: Feldman, Sara. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina |
Databáze: | OpenAIRE |
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