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Boron Neutron Capture Synovectomy

  • Jacquelyn C. Yanch
Chapter

Abstract

Use of the boron neutron capture reaction is a potential means of treating the symptoms of rheumatoid arthritis and related diseases. For this approach, termed boron neutron capture synovectomy (BNCS), the goal is cellular ablation within the inflamed synovium, the membrane lining the inner surface of the joint capsule of all articulating joints. To be effective in destroying the synovial membrane, radiation doses must be very large (approximately 100 Gy in a single delivery), substantially higher than those used in BNCT of tumors where cessation of reproductive capability in malignant cells is the clinical goal. Generating large radiation doses requires that very high boron concentrations be present in the target tissue at the time of irradiation. While it is unlikely that systemic administration of the boron compound can result in the needed synovial boron concentrations, extremely high boron levels can be readily achieved via local delivery, that is, by injection of the compound directly into the joint fluid. This delivery approach results in very high synovial boron levels in vivo, which means that radiation treatment times can be very short. Neutron beams based on accelerator, reactor, and isotope sources have been designed at many institutions around the world, and in some cases, these beams have been built and experimentally characterized. With existing neutron sources, human joint irradiations could be performed in a matter of minutes. The efficacy of BNCS in causing synovial necrosis has been clearly demonstrated in an animal model of arthritis. However, the boron compound used for this study was found to freely enter the articular cartilage leading to unequivocal histological evidence of cartilage damage following neutron irradiation of the joint. The continued development of BNCS as a viable clinical modality thus awaits the identification and testing of an alternative boron-labeled compound, one that will be excluded, perhaps on the basis of physical size, from the cartilage.

Keywords

Synovial Membrane Neutron Beam Neutron Capture Capture Cross Section Boron Compound 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Tehlirian CV, Bathon JM (2008) Rheumatoid arthritis A. Clinical and laboratory manifestations. In: Klippel JH, Stone JH, Crofford LJ, While PH (eds) Primer on the rheumatic diseases, 13th edn. Springer, New YorkGoogle Scholar
  2. 2.
    Ishikawa H, Osamu O, Hirohata K (1986) Long–term results of synovectomy in rheumatoid patients. J Bone Joint Surg 68A:198–205Google Scholar
  3. 3.
    Matsui N, Taneda Y, Ohta H, Itoh T, Tsuboguchi S (1989) Arthroscopic versus open synovectomy in the rheumatoid knee. Int Orthop 13:17–20PubMedCrossRefGoogle Scholar
  4. 4.
    Klug S, Wittmann G, Weseloh G (2000) Arthroscopic synovectomy of the knee joint in early cases of rheumatoid arthritis: follow-up results of a multicenter study. Arthroscopy 16:262–7PubMedCrossRefGoogle Scholar
  5. 5.
    Kresnik E, Mikosch P, Gallowitsch HJ, Jesenko R, Just H, Kogler D, Gasser J, Heinisch M, Unterweger O, Kumnig G, Gomez I, Lind P (2002) Clinical outcome of radiosynoviorthesis: a meta-analysis including 2190 treated joints. Nucl Med Commun. 23(7):683–8PubMedCrossRefGoogle Scholar
  6. 6.
    Deutsch E, Brodack JW, Deutch KR (1993) Radiation synovectomy revisited. Eur J Nucl Med 20:1113–1127PubMedCrossRefGoogle Scholar
  7. 7.
    Delbarre F, Menkes CJ (1974) Non-surgical synovectomy in rheumatoid arthritis. Results obtained by radio-synoviorthesis. Adv Clin Pharmacol 6:134–9PubMedGoogle Scholar
  8. 8.
    Nemec HW, Fridrich R (1977) Retention and dosage in radiation synovectomy with yttrium-90-silicate colloid. Nuklearmedizin 16:113–8PubMedGoogle Scholar
  9. 9.
    Hall EJ (1994) Radiobiology for the radiologist, 4th edn. J.B. Lippincott Company, Philadelphia, p 30Google Scholar
  10. 10.
    de la Chapelle A, Oka M, Rekonen A, Ruotsi A (1972) Chromosome damage after intra-articular injections of radioactive yttrium. Ann Rheum Dis 1:508–12CrossRefGoogle Scholar
  11. 11.
    Lloyd DC, Reeder EJ (1978) Chromosome aberrations and intra-articular yttrium-90. Lancet 1:617PubMedCrossRefGoogle Scholar
  12. 12.
    Yanch JC, Shortkroff S, Shefer RE, Johnson S, Binello E, Gierga D, Jones AG, Young G, Vivieros C, Davison A and Sledge C (1999) Boron Neutron Capture Synovectomy: Treatment of Rheumatoid Arthritis Based on the 10B(n,a)7Li Nuclear Reaction. Medical Physics, (26)3:364–375Google Scholar
  13. 13.
    Johnson LS, Yanch JC, Shortkroff S, Sledge C (1996) Temporal and spatial distribution of boron uptake in excised human synovium. In: Mishima Y (ed) Cancer neutron capture therapy. Plenum Press, New York, pp 183–188Google Scholar
  14. 14.
    Binello E, Yanch JC, Shortkroff S, Vivieros C, Yound G, Jones AG, Sledge CB, Davidson A (1997) In vitro analysis of 10B uptake for boron neutron capture synovectomy. In: Advances in neutron capture therapy, vol II. Elsevier, Amsterdam, pp 609–613Google Scholar
  15. 15.
    Yanch JC, Shortkroff S, Shefer RE, Binello E, Gierga D, Jones AG, Young G, Vivieros C, Blackburn B (2001) Progress in the development of boron neutron capture synovectomy for the treatment of rheumatoid arthritis. In: Hawthorne MF, Shelly K, Wiersema RJ (eds) Frontiers in neutron capture therapy. Kluwer Academic, New York, pp 1389–1397CrossRefGoogle Scholar
  16. 16.
    Binello E, Ly A, Yanch JC and Shortkroff S (1996) Monte Carlo Investigation of Optimal Neutron Beam Energy for Boron Neutron Capture Synovectomy. Radiation Protection and Shielding (American Nuclear Society, La Grange Park, IL) Vol. 2, 659–664Google Scholar
  17. 17.
    Gierga DP, Yanch JC and Shefer RE (2000) Development and construction of a neutron beam line for accelerator-based boron neutron capture synovectomy. Medical Physics, 27(1):203–214PubMedCrossRefGoogle Scholar
  18. 18.
    Verbeke JM, Chen AS, Vujic JS, Leung K (2001) Optimization of Beam-Shaping Assemblies for BNCS Using the High-Energy Neutron Sources D-D and D-T, Nuclear Technology 134(3), 278–293Google Scholar
  19. 19.
    Berlizov AM, Razbudey VF, Shevchenko YB, Tryshyn VV (2006) Prospects of Neutron Capture Synovectomy at Thermal Nuclear Reactors. Nuclear Physics and Atomic Energy, 1, p 67–72Google Scholar
  20. 20.
    Wu J, Chang SJ, Chuang KS, Hsueh YW, Yeh KC, Wang JN, Tsai WP (2007) Dose evaluation of boron neutron capture synovectomy using the THOR epithermal neutron beam: a feasibility study. Phys Med Biol. 52(6):1747–1756PubMedCrossRefGoogle Scholar
  21. 21.
    Abdalla K, Naqvi AA, Maalej N, Elshahat B (2010) Dose calculation from a D-D-reaction-based BSA for boron neutron capture synovectomy. Appl Radiat Isot. Apr–May;68(4–5):751–754Google Scholar
  22. 22.
    Vega-Carrillo HR and Manzanares-Acuña E (2003) Neutron Source for Boron Neutron Capture Synovectomy. Alasbimn Journal 5(21)Google Scholar
  23. 23.
    Gierga, DP (2001) Neutron Delivery for Boron Neutron Capture Synovectomy. Ph.D. dissertation, Massachusetts Institute of TechnologyGoogle Scholar
  24. 24.
    Gierga DP, Yanch JC and Shefer RE (2000) An investigation of the feasibility of gadolinium for neutron capture synovectomy. Medical Physics, 27(7):1685–1692PubMedCrossRefGoogle Scholar
  25. 25.
    Shortkroff S, Binello E, Zhu X, Gierga D, Thornhill TS, Shefer R, Jones AG and Yanch JC (2004) Dose Response of the AIA Rabbit Stifle Joint to Boron Neutron Capture Synovectomy. Nucl. Med. Biol. 31(5):663–670PubMedCrossRefGoogle Scholar
  26. 26.
    Watson-Clark RA, Banquerigo ML, Shelly K, Hawthorne MF, and Brahn E (1998) Model studies directed toward the application of boron neutron capture therapy to rheumatoid arthritis: Boron delivery by liposomes in rat  collagen-induced  arthritis. PNAS 95(5)2531–2534PubMedCrossRefGoogle Scholar
  27. 27.
    Valliant JF, Schaffer P (2001) A new approach for the synthesis of isonitrile carborane derivatives. Ligands for metal based boron neutron capture therapy (BNCT) and boron neutron capture synovectomy (BNCS) agents. J Inorg Biochem. 85(1):43–51Google Scholar
  28. 28.
    Valliant, JA, Schaffer P, Britten JF, Davison A, Jones AG and Yanch JC (2000) The synthesis of corticosteroid-carborane esters for the treatment of rheumatoid arthritis via boron neutron capture synovectomy. Tetrahedron Letters, 41:1355–1358CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Departments of Nuclear Science and Engineering and Biological EngineeringMassachusetts Institute of TechnologyCambridgeUSA

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