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Boron neutron capture synovectomy (BNCS) as a potential therapy for rheumatoid arthritis: boron biodistribution study in a model of antigen-induced arthritis in rabbits

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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 10B), (b) GB-10 (5 mg 10B), (c) GB-10 (50 mg 10B) and intravenous (iv), (d) BPA-f 0.14 M (15.5 mg 10B/kg), (e) GB-10 (50 mg 10B/kg), and (f) BPA-f (15.5 mg 10B/kg) + GB-10 (50 mg 10B/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.

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Acknowledgments

This study was partially supported by grants from the Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT) and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina. GB-10 was kindly provided by Dr. David W. Nigg of Idaho National Laboratory, USA. The authors wish to acknowledge Dr. JC Yanch for her inspiring work.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Radiobiology, Comisión Nacional de Energía Atómica (CNEA), Avenida General Paz 1499, B1650KNA, San Martin, Provincia de Buenos Aires, Argentina

    Verónica A. Trivillin, Marcela A. Garabalino, Andrea Monti Hughes, Elisa M. Heber & Amanda E. Schwint

  2. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Argentina

    Verónica A. Trivillin, Sara Feldman & Amanda E. Schwint

  3. LABOATEM (Laboratorio de Biología Osteoarticular, Ingeniería Tisular y Terapias Emergentes), Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina

    David B. Abramson, Gaston E. Bumaguin, Leandro J. Bruno & Sara Feldman

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  1. Verónica A. Trivillin
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  2. David B. Abramson
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  3. Gaston E. Bumaguin
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  5. Marcela A. Garabalino
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  6. Andrea Monti Hughes
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  9. Amanda E. Schwint
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Correspondence to Amanda E. Schwint.

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Trivillin, V.A., Abramson, D.B., Bumaguin, G.E. et al. Boron neutron capture synovectomy (BNCS) as a potential therapy for rheumatoid arthritis: boron biodistribution study in a model of antigen-induced arthritis in rabbits. Radiat Environ Biophys 53, 635–643 (2014). https://doi.org/10.1007/s00411-014-0564-3

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