title: Boron neutron capture synovectomy (BNCS) as a potential therapy for rheumatoid arthritis: boron biodistribution study in a model of antigen-induced arthritis in rabbits.
abstract: Boron neutron capture synovectomy (BNCS) is explored for the treatment of rheumatoid arthritis (RA). The aim of the present study was to perform boron biodistribution studies in a model of antigen-induced arthritis (AIA) in female New Zealand rabbits, with the boron carriers boronophenylalanine (BPA) and sodium decahydrodecaborate (GB-10) to assess the potential feasibility of BNCS for RA. Rabbits in chronic phase of AIA were used for biodistribution studies employing the following protocols: intra-articular (ia) (a) BPA-f 0.14 M (0.7 mg (10)B), (b) GB-10 (5 mg (10)B), (c) GB-10 (50 mg (10)B) and intravenous (iv), (d) BPA-f 0.14 M (15.5 mg (10)B/kg), (e) GB-10 (50 mg (10)B/kg), and (f) BPA-f (15.5 mg (10)B/kg) + GB-10 (50 mg (10)B/kg). At different post-administration times (13-85 min for ia and 3 h for iv), samples of blood, pathological synovium (target tissue), cartilage, tendon, muscle, and skin were taken for boron measurement by inductively coupled plasma mass spectrometry. The intra-articular administration protocols at <40 min post-administration both for BPA-f and GB-10, and intravenous administration protocols for GB-10 and [GB-10 + BPA-f] exhibited therapeutically useful boron concentrations (>20 ppm) in the pathological synovium. Dosimetric estimations suggest that BNCS would be able to achieve a therapeutically useful dose in pathological synovium without exceeding the radiotolerance of normal tissues in the treatment volume, employing boron carriers approved for use in humans. Radiobiological in vivo studies will be necessary to determine the actual therapeutic efficacy of BNCS to treat RA in an experimental model.
authors.affiliation: Department of Radiobiology, Comisión Nacional de Energía Atómica (CNEA), Avenida General Paz 1499, B1650KNA, San Martin, Provincia de Buenos Aires, Argentina, trivilli@cnea.gov.ar.
authors.forename: Verónica A
authors.initials: VA
authors.lastname: Trivillin
authors.forename: David B
authors.initials: DB
authors.lastname: Abramson
authors.forename: Gaston E
authors.initials: GE
authors.lastname: Bumaguin
authors.forename: Leandro J
authors.initials: LJ
authors.lastname: Bruno
authors.forename: Marcela A
authors.initials: MA
authors.lastname: Garabalino
authors.forename: Andrea
authors.initials: A
authors.lastname: Monti Hughes
authors.forename: Elisa M
authors.initials: EM
authors.lastname: Heber
authors.forename: Sara
authors.initials: S
authors.lastname: Feldman
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Schwint
mesh_terms: D000818:Animals; D000941:Antigens / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000139:chemically induced* / Q000628:therapy*; D001895:Boron / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001896:Boron Compounds / Q000493:pharmacokinetics; D016754:Boron Neutron Capture Therapy; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D011817:Rabbits; D014018:Tissue Distribution
chemical_list: C089739:4-boronophenylalanine-fructose; D000941:Antigens; D001896:Boron Compounds; C569622:decahydrodecaborate; D005632:Fructose; D001895:Boron