Neutron capture therapy

Thermal neutrons are desired at the tumour location because the B interaction probability is much higher with slower neutrons. Therefore, surface or shallow tumours can be irradiated with thermal neutrons, while those at a depth of a few centimetres can be irradiated with epithermal neutrons which then become thermalized by the overlying tissue. Thermal neutrons are also useful for research involving cell cultures or small animal irradiations. 

As currently practiced, most neutron capture therapy makes use of boron compounds however, other compounds (e.g., gadolinium compounds) can also be used. 

It should be emphasized that NCT is still in the research phase with no Phase HI clinical trials having yet been performed. In addition, it has been concluded that the results of 320 patients treated in BNCT studies have not demonstrated any significant benefit for these patients. 

Current research efforts are directed toward providing the dose to the tumour in a short time period (minutes instead of hours) and reducing the dose to normal tissue through higher flux, better neutron energy selectors, shielding and collimation and better drugs. 

BNCT research varies in several aspects from one treatment centre to another as follows  

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Various borate esters are chemostetilants for house flies (51). Tributyl borate, available from Eagle-Picher, Miami, Oklahoma, which is isotopically enriched in boron-10, is being used as a chemical precursor in the synthesis of pharmacologically active boron compounds suitable for boron neutron capture therapy. 

One of the most promising appHcations of polyboron hydride chemistry is boron neutron capture therapy (BNCT) for the treatment of cancers (253). Boron-10 is unique among the light elements in that it possesses an unusually high neutron capture nuclear cross section (3.8 x 10 , 0.02—0.05 eV... 

To date, the most extensively studied polyboron hydride compounds in BNCT research have been the icosahedral mercaptoborane derivatives Na2[B22H22SH] and Na [(B22H22S)2], which have been used in human trials with some, albeit limited, success. New generations of tumor-localizing boronated compounds are being developed. The dose-selectivity problem of BNCT has been approached using boron hydride compounds in combination with a variety of deUvery vehicles including boronated polyclonal and monoclonal antibodies, porphyrins, amino acids, nucleotides, carbohydrates, and hposomes. Boron neutron capture therapy has been the subject of recent reviews (254). 

Polyhedral Boron Hydrides. These are used in neutron capture therapy of cancers (254), and as bum rate modifiers (accelerants) in gun and rocket propellant compositions. 

Metallacarboranes. These are used in homogeneous catalysis (222), including hydrogenation, hydrosilylation, isomerization, hydrosilanolysis, phase transfer, bum rate modifiers in gun and rocket propellants, neutron capture therapy (254), medical imaging (255), processing of radioactive waste (192), analytical reagents, and as ceramic precursors. 

H. Hatanaka, Boron-Neutron Capture Therapy for Tumors, Nishimura Co., Ltd., Niigata, Japan, 1986. 

Amine boranes have been examined by a variety of spectroscopic methods (24—29). The boron-substituted alpha-amino acids have been utilized in animal model studies. These compounds along with their precursors and selected derivatives have been shown to possess antineoplastic, antiarthritic, and hypolipidemic activity (30—32). The boron amino acid analogues are also being evaluated for possible utility in boron neutron capture therapy (BNCT) (33). 

H. Hatanaka, Boron Neutron Capture Therapy for Tumours, Nishimura, Niigata, Japan, 1986. R. G. Fairchild, V. P. Bond and A. D. Woodhead (eds.). Clinical Aspects of Neutron Capture Therapy, Plenum, New York, 1989, 370 pp. °M. F. Hawthorne, PureAppl. Chem. 63, 327-34 (1991). 

B. J. Allen, D. E. Moore and B. V. Harrington (eds.). Progress in Neutron Capture Therapy for Cancer (Proc. 4th Intemat. Conf.), Plenum, New York, 1992, 668 pp. 

Synthesis of boron heterocycles for neutron capture therapy 94YGK1044. 

Several kinds of cancer therapy use radiation to destroy malignant cells. Boron neutron capture therapy is unusual in that boron-10, the isotope injected, is not radioactive. However, when boron-10 is bombarded with neutrons, it gives off highly destructive a particles. In boron neutron capture therapy, the boron-10 is incorporated into a compound that is preferentially absorbed by tumors. The patient is then exposed to brief periods of neutron bombardment. As soon as the bombardment ceases, the boron-10 stops generating a particles. 

Born interpretation, 17 Born-Haber cycle, 252 Born-Meyer equation, 64 borohydride, 602 boron, 47, 599 boron configuration, 34 boron neutron capture therapy, 708 boron nitride, 601 boron trifluoride, 77, 98,106 borosilicate glass, 616 Bosch, C, 357, 386 bottom-up, 648... 

Boro nophenyl) alanine (BPA) is a practical boron compound which is clinically used for the treatment of not only malignant melanoma but also of brain tumors, in neutron capture therapy (Scheme 1-40) [105, 152, 153]. Although (pinacolato)di-boron (82) is an excellent reagent to afford the corresponding boronate in 88% yield, it strongly resists the hydrolysis to arylboronic acids. Alternatively, the 1,3-diphenyl-propanediol ester (85) is more convenient to deprotect the diol moiety by catalytic hydrogenolysis [105]. 

Much attention has recently been focused on organoboronic acids and their esters because of their practical usefulness for synthetic organic reactions including asymmetric synthesis, combinatorial synthesis, and polymer synthesis [1, 3, 7-9], molecular recognition such as host-guest compounds [10], and neutron capture therapy in treatment of malignant melanoma and brain tumor ]11]. New synthetic procedures reviewed in this article wiU serve to find further appHcations of organoboron compounds. 

Sessler, J. L. Allen, W. E. Krai, V. A. Preparation of highly boronated derivatives of expanded porphyrins (texaphyrins) for potential use in boron neutron capture therapy and related applications. US Patent 5,955,586, 1999 Chem. Abstr. 1999, 131, 222611. 

Alam, F., Soloway, A.H., Barth, R.F., Mafune, N., Adams, D.M., and Knoth, W.H. (1989) Boron neutron capture therapy Linkage of a boronated macromolecule to monoclonal antibodies directed against tumor-associated antigens./. Med. Chem. 32, 2326-2330. 

Holmberg, A., and Meurling, F. (1993) Preparation of sulfhydrylhorane-dextran conjugates for boron neutron capture therapy. Bioconjugate Chem. 4, 570-573. 

Shukla, S., Wu, G., Chatterjee, M., Yang, W., Sekido, M., Diop, L.A., Muller, R., Sudimack, J.J., Lee, R.J., Barth, R.F., and Tjarks, W. (2003) Synthesis and biological evaluation of folate receptor-targeted boro-nated PAMAM dendrimers as potential agents for neutron capture therapy. Bioconjugate Chem. 14, 158-167. 

B-scan recording, 17 425 BSH, reagent for boron neutron capture therapy, 4 190, 227 B-staged adhesives, 1 528 Bt cottons, 8 2... 

The doso-duster containing two carbon atoms, i.e., o-, m- or p-dicarba-doso-dodecaborane C2B10H12, is electronically neutral (see Chapter 3.2). Therefore, the cages are thermally and chemically stable, and extremely hydrophobic. The C2Bio cages are advantageous for boron neutron capture therapy (BNCT) because of their high boron content and ease of chemical transformation. 

Carpenter, Advances in Neutron Capture Therapy, Plenum Press, New York, 1993. 

T. Peymann, D. Preusse, D. Gabel, in Advances in Neutron Capture Therapy, Volume II, Chemistry and Biology, B. Larsson, J. Crawford, R. 

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