Analysis of in Vivo Uptake for Boron Neutron Capture Synovectomy

Binello, Emanuela; Shortkroff, Sonya; Shefer, R. E.; Jones, Alun G.; Davison, Alan; Thornhill, Thomas S.; Yanch, J. C.

doi:10.1007/978-1-4615-1285-1_162

Cited by 8 publications

(11 citation statements)

References 6 publications

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“…13,22,23 Intense neutron moderation is needed for any accelerator based neutron source. Low-Z elements ͑such as 2 H or 1 H) are most effective as neutron moderators.…”

Section: Geometry and Materials Of Moderator/reflector Assemblymentioning

confidence: 99%

“…This range of 10 B concentration was based on in vivo uptake studies using arthritic rabbits which showed that boron levels of up to 19 000 ppm are achievable in the synovium. 12 Boron tissue concentrations were explicitly included in the Monte Carlo simulations.…”

Section: F Effects Of 10 B Uptake In Synoviummentioning

confidence: 99%

“…Second, in vivo 10 B uptake studies have indicated that boron levels in the synovium on the order of thousands of ppm are achievable. 12 In BNCS, the boron-labeled compound is injected directly into the fluid adjacent to the target tissue. In BNCT, conversely, the boronated compound is delivered systemically, so 10 B levels in the target tissue are significantly lower, usually on the order of 30-40 ppm.…”

Section: Introductionmentioning

confidence: 99%

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Development and construction of a neutron beam line for accelerator‐based boron neutron capture synovectomy

2000

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A potential application of the 10B(n, alpha)7Li nuclear reaction for the treatment of rheumatoid arthritis, termed Boron Neutron Capture Synovectomy (BNCS), is under investigation. In an arthritic joint, the synovial lining becomes inflamed and is a source of great pain and discomfort for the afflicted patient. The goal of BNCS is to ablate the synovium, thereby eliminating the symptoms of the arthritis. A BNCS treatment would consist of an intra-articular injection of boron followed by neutron irradiation of the joint. Monte Carlo radiation transport calculations have been used to develop an accelerator-based epithermal neutron beam line for BNCS treatments. The model includes a moderator/reflector assembly, neutron producing target, target cooling system, and arthritic joint phantom. Single and parallel opposed beam irradiations have been modeled for the human knee, human finger, and rabbit knee joints. Additional reflectors, placed to the side and back of the joint, have been added to the model and have been shown to improve treatment times and skin doses by about a factor of 2. Several neutron-producing charged particle reactions have been examined for BNCS, including the 9Be(p,n) reaction at proton energies of 4 and 3.7 MeV, the 9Be(d,n) reaction at deuteron energies of 1.5 and 2.6 MeV, and the 7Li(p,n) reaction at a proton energy of 2.5 MeV. For an accelerator beam current of 1 mA and synovial boron uptake of 1000 ppm, the time to deliver a therapy dose of 10,000 RBEcGy ranges from 3 to 48 min, depending on the treated joint and the neutron producing charged particle reaction. The whole-body effective dose that a human would incur during a knee treatment has been estimated to be 3.6 rem or 0.75 rem, for 1000 ppm or 19,000 ppm synovial boron uptake, respectively, although the shielding configuration has not yet been optimized. The Monte Carlo design process culminated in the construction, installation, and testing of a dedicated BNCS beam line on the high-current tandem electrostatic accelerator at the Laboratory for Accelerator Beam Applications at the Massachusetts Institute of Technology.

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“…13,22,23 Intense neutron moderation is needed for any accelerator based neutron source. Low-Z elements ͑such as 2 H or 1 H) are most effective as neutron moderators.…”

Section: Geometry and Materials Of Moderator/reflector Assemblymentioning

confidence: 99%

Section: F Effects Of 10 B Uptake In Synoviummentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Development and construction of a neutron beam line for accelerator‐based boron neutron capture synovectomy

2000

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“…Further tests were carried out to determine its minimum residence time in synovial tissue by performing a ''washout'' study. 21 Samples of human arthritic synovium were incubated in medium containing approximately 1000 ppm 10 B in unenriched ͑i.e., 5000 ppm elemental boron͒ K 2 B 12 H 12 for one hour. ͑Note that since natural boron contains roughly 20% 10 B, 1000 ppm 10 B represents approximately 5000 ppm elemental boron.…”

Section: A 10 B Uptake Measurements Ex Vivomentioning

confidence: 99%

“…Unlike BNCT, however, our research to date suggests that large concentrations of 10 B can be delivered to the target tissue in BNCS. [17][18][19][20][21] Large 10 B concentrations within the target tissue coupled with the fact that the synovium is located 0.5-1.5 cm below the skin surface leads to neutron beam requirements that differ considerably from those of BNCT.…”

Section: Introductionmentioning

confidence: 99%

Boron neutron capture synovectomy: Treatment of rheumatoid arthritis based on the nuclear reaction

Yanch¹,

Shortkroff

Shefer

et al. 1999

Medical Physics

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A novel application of the 10 B(n,␣) 7 Li nuclear reaction for the treatment of rheumatoid arthritis is under investigation. Rheumatoid arthritis is characterized by a painful inflammation of the membrane ͑synovium͒ lining articular joints. Since the tissue targeted for treatment is the diseased synovial membrane and the goal is synovial ablation ͑''synovectomy''͒, the proposed treatment is called Boron Neutron Capture Synovectomy. Development of this therapeutic modality has been carried out in a number of areas, including the ex vivo and in vivo evaluation of 10 B in arthritic synovium, and the design and construction of a dedicated neutron beam assembly for joint irradiation. Ex vivo evaluation of boron uptake in human arthritic synovium using K 2 B 12 H 12 has demonstrated that 10 B concentrations of 550-2400 ppm are repeatedly obtained. Preliminary in vivo experiments in an arthritic rabbit model have shown that synovial boron concentrations of approximately 265-950 ppm are obtained at 15 min post intra-articular injection. With these uptake levels experimental evaluation of the efficacy of BNCS in the treatment of rheumatoid arthritis in an animal model can be carried out. Optimal neutron beams suitable for joint irradiation are shown to be lower in energy than those used for BNCT. An assembly comprising a graphite reflector surrounding a D 2 O moderator has been designed, constructed, and installed on the 4.1 MeV tandem electrostatic accelerator at MIT's Laboratory for Accelerator Beam Applications. Monte Carlo calculations predict a total therapy time of between 8.4 and 31 min for the human knee, depending on the charged particle reaction used; a particle beam current of 1 mA is assumed. Therapy times to treat a human finger joint range from 4 to 14 min for a 1 mA accelerator current. These treatment times are based on average 10 B in vivo uptake levels ͑observed experimentally in the rabbit knee͒ of 950 ppm and a 10 000 RBE-cGy treatment dose. It is concluded that Boron Neutron Capture Synovectomy, consisting of intra-articular injection of a 10 B-labeled compound followed by neutron irradiation of the joint, has considerable potential as a means of treating rheumatoid arthritis.

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Progress in the Development of Boron Neutron Capture Synovectomy for the Treatment of Rheumatoid Arthritis

Yanch¹,

Shortkroff

Shefer

et al. 2001

Frontiers in Neutron Capture Therapy

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Analysis of in Vivo Uptake for Boron Neutron Capture Synovectomy

Cited by 8 publications

References 6 publications

Development and construction of a neutron beam line for accelerator‐based boron neutron capture synovectomy

Development and construction of a neutron beam line for accelerator‐based boron neutron capture synovectomy

Boron neutron capture synovectomy: Treatment of rheumatoid arthritis based on the nuclear reaction

Progress in the Development of Boron Neutron Capture Synovectomy for the Treatment of Rheumatoid Arthritis

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