Boron neutron captures therapy

For more than a half century now Boron Neutron Capture Therapy (BNCT) has had potential as a treatment against cancers in difficult-to-access areas of the body. Targets are principally maUgnant brain tumors called glioblastoma multiformehvX also include head and neck cancers involving the Up, mouth, nasal cavities, lymph nodes, sinuses, pharynx, and larynx. How does BNCT work As we know from Table 14.2, boron has two important isotopes, boron-11 (80.22%) and boron-10 (19.78%). It turns out that when B-10 is bombarded with slow or so-called thermal neutrons, an excited, unstable form of boron-11 is formed that immediately disintegrates to produce alpha particles and lithium-7. This process is shown in Equation 14.18. 

The alpha particles are highly energetic but do not travel far in the body. Consequently, they would be useful against carcinomas in the immediate vicinity around the boron nuclei. This precise targeting is important because the therapy needs to be specific to the cancer cells while sparing the surrounding normal tissues. 

Given the above nuclear process, there are two requirements for successful BNCT. The first is access to a source of thermal neutrons. At present these are only available using a nuclear reactor, but particle accelerators may soon serve as an 

Several carbaboranes already described have been studied with the aim of accessing compounds that of use in BCNT. 87.102 This section reviews work that is specifically targetted at studies related to BNCT. The synthesis of carboranylmethyl ethers of steroids has been reported steroidal 2-propynoxy derivatives have been inserted into 6,9-Ws(acetonitrile)-decaborane(12). These reactions give new compounds containing estrane and androstane skeletons which are 

Componds such as (25) have been prepared in high yield by linking c/o.ro-C2Bio-clusters with nitroimidazoles the precursors are m-alkenyl and (U-alkynyl-2-nitroimidazoles and carbaborane nitrile oxide. The lipophilic nature some of the new conqtlexes has been noted. Aminoalkyl-derivatives of C/050-C2B10H12 have been reported. The functional groups allow the carbaboranes to be incorporated into structures that are of potential use in BNCT. A range of other functionalised carbaborane clusters have been prepared for example, the attachment of 

KOster, G. Seidel and HJ. Hors chafer./nora. Synth., 1992,29.83. 

Tseung, D. Tran, M. Conea, S. Henaaand J. Anas, Inorg. Chem., 1992,31,2161. 

Enders.H.Mukow and WSiebeit.Angim. CAmi.,/iir. il ngf., 1992,3X606. 

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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). 

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). 

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... 

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. 

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. 

Yinghuai Z, Peng AT, Carpenter K, Maguire JA, Hosmane NS, Takagaki M (2005) Substituted carborane-appended water-soluble single-wall carbon nanotubes New approach to boron neutron capture therapy drug delivery. J. Am. Chem. Soc. 127 9875-9880. 

Johnsson M, Bergstrnd N, Edwards K. Optimization of drug loading procedures and characterization of liposomal formulations of two novel agents intended for boron neutron capture therapy (BNCT). J Liposome Res 1999 9 53-79. 

Drug and DNA delivery, photodynamic therapy, boron neutron capture therapy, and magnetic resonance imaging are some areas in which appropriately functionalized dendrimers are being evaluated (Jang and Kataoka 2005 Svenson and Tomalia 2005 Yang and Kao 2006). In one particularly nice example, polylysine... 

For historical reasons and for their general principles, pion therapy and the still experimental Boron Neutron Capture Therapy are also briefly discussed. 

In conclusion, boron neutron capture therapy (BNCT) is still in an experimental phase. Although the rationale is particularly attractive (selectivity at the cellular level), it is difficult to draw conclusions from the available clinical data. 

Porphyrins are chromophores, occurring in diverse molecules, such as hemoglobin and chlorophyll. They have a propensity to accumulate in tumors (81). Boronated porphyrins or their derivatives have great potential as boron carriers in boron neutron capture therapy (82). 

Modification of depolymerization kinetics and release Endosomal escape Nonviral gene delivery Boron neutron capture therapy Fusogenic liposomes, increase transfection efficiency... 

Barth RF. A critical assessment of boron neutron capture therapy an overview. J Neuro Oncol 2003 62 1-5. 

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