Tumor therapy, boron neutron capture

The incorporation of a large number of boron atoms into a tumor for boron neutron capture therapy (BNCT) has been accorded considerable interest over the last few years [67]. It is known that if boron-containing cells are exposed to a neutron flux, they are destroyed without causing irreparable harm to adjacent healthy tissue. In the context of SERMs, for example, Endo et al. have prepared complex 18 [ 1 - (hydroxymethyl) -12- (4-hydroxyphenyl) -1,12-dicarba-closo-dodeca-borane] in which the hydrophobic carborane cage mimics the C and D rings of estradiol (Scheme 3.7) [68]. 

Lu, D. R. Mehta, S. C. Chen, W., Selective boron drug delivery to brain tumors for boron neutron capture therapy. A fv. Drug Deliv. Rev. 1997, 26, 231-247. 

Destruction of Tumors Using Boron Neutron Capture Therapy (BNCT)—... 

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. 

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. 

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. 

Boron seems to have an affinity for cancerous tumors, and this property has been exploited in radiation therapy (Hamada et al. 1983 Hatanaka 1986). Boron-10 has been used in neutron capture therapy to cure malignant sarcomas implanted in the hind legs of mice, as well as spontaneous malignant melanomas in pigs (Slatkin etal. 1986). The sulfhydral borane monomer (Bi2HnSH) is used as a B-10 carrier in neutron therapy of malignant human brain tumors and seems to be most effective at 30 pg B-lO/kg tissue (Hatanaka 1986). Polyhedral boranes attached to monoclonal antibodies that are tumor specific may become useful in tumor therapy by neutron irradiation (Parry... 

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). 

Boron neutron capture therapy of primary and metastatic brain tumors. [R. F. Barth, A. H. Soloway, Mol. Chem. Neuropathol. 1994, 27(2-3), 139-154] [ 1863]. 

The dual-mechanism of cytotoxic activity of amine-boranes, possessing significant antineoplastic activity and useful also in boron neutron capture therapy (BNCT), initiated the search during recent years for therapeutic compounds of this class which accumulate preferentially in the tumor tissue194,195. The title compound 192, one of the... 

In work that also involves the use of a Mn(III) porphyrin, Huang et al. published a report on the manganese chelate of the tetrakiscarborane carboxylate ester of 2,4-(a, P-dihydroxylethyl)deuteroporphyrin IX (MnBOPP, 9, Figure 2) [19]. The free-base form of this derivative, BOPP, has demonstrated potential as an agent for boron neutron capture therapy (BNCT) [75,76] and photodynamic therapy (PDT) [77] and is known to localize selectively in cerebral glioma tumors at ratios as high as 400 1 relative to normal brain tissue [19,78]. Like the free-base, MnBOPP also selectively localizes in tumor tissue. Specifically, it has been shown to enhance preferentially the... 

Carboranes in Boron Neutron Capture Therapy of Cancer (B7YC2). The stable isotope of boron, B (19.8% natural abundance), is very effective as a neutron capture agent with the effective nuclear cross section of 3837 bams, while the "B nucleus is incapable of undergoing a BNC reaction. Therefore, the B-emiched carborane and borane-substituted biomolecules and dmgs are selectively dehvered to the cancer cells in the human body and then the tumor-localized B nucleii are bombarded with either thermal or epithermal neutrons that results in a fission reaction producing the high energy alpha (a) particles as shown in equation (2). 

Successful treatment of tumors by radiation therapy demands that the dose ratio between tumor tissue and surrounding healthy tissue is greater than unity, and that the radiation dose to the healthy tissue approaches the tolerance dose. This requirement is generally achieved in conventional radiotherapy when applied successfully. It must also be fulfilled in boron neutron capture therapy (BNCT). 

Gabel, D. Boron neutron capture therapy of tumors Principles, problems and perspectives. Adv. Tech. Radiother. 85-115,1992. 

Boron has two stable isotopes, (80.4% abundance) and °B (19.6%). B has a very high neutron absorption cross section (it is a good absorber of neutrons). This property has been developed for use in the treatment of cancerous tumors in a process called boron neutron capture therapy (BNCT). Boron-containing compounds having a... 

Carboranes are particular cyclic spacers that have been introduced for boron neutron capture therapy to be taken up by tumor cells [295,296,297]. Aromatic spacers have been integrated in cyclodextrin analogues to modify the guest binding properties [298,299,300]. Also amide-linked polymeric open chain sugars with aromatic spacers were prepared [257,264,301]. Sugars with cyclic spacers are also found in Nature [302], well known examples are antibiotics such as calicheamicin [303,304] or vancomicin [305]. 

Miura M, Micca PL, Fisher CD, et al. Synthesis of a nickel tetracarbonylphenylporphyrin for boron neutron-capture therapy biodistribution and toxicity in tumor-bearing mice. Int J Cancer 1996 68 114-119. 

Boron is an essential trace element for plants and is beneficial for animals and humans. Dietary boron obviously plays a role in immune functions. Among the best-known natural boron-containing compounds are polyketide antibiotics such as boromycin, aplasmomycins, borophycin and tatrolons. Attempts are underway to incorporate boron into different biologically active molecules, particularly for medicinal application, e.g. for boron neutron capture therapy of brain tumors. Some boron-containing biomolecules may apparently act as signaling molecules that interact with cell surfaces. 

Gabel, D. Tumor-seeking for boron neutron capture therapy synthesis and biodistribution. Basic Life Sci. 1989, 50, 233-241. 

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