Neutron capture approach

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). 

Measurements of " Th in sediment samples (Aller and Cochran 1976 Cochran and Aller 1979) used much the same approach as outlined above. In this case, the dried sediment sample ( 10 g) was leached with strong mineral acid (HCl) in the presence of a yield monitor (generally Th, an artificial Th isotope resulting from the decay of Th that is produced by neutron capture on Th). Thorium was separated from U and purified by ion exchange chromatography, and electrodeposited onto stainless steel planchets. Counting and determination of " Th activity followed the procedure outlined above. 

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. 

Undoubtedly the most unlikely substrate for ferritin is U02 +, however, the imphcations of biomimetically synthesizing uranium oxide loaded ferritin could have use in neutron capture therapy. The synthetic approach utilized ion binding of U02(02CCH3)2 according to a known stoichiometry of 12 ions per ferritin molecule, followed by hydrolytic polymerization of metal ions within apo-ferritin. Characterization by TEM analysis confirmed dense cores of polymerized uranyl oxyhydroxide particles of 6 nm in diameter. 

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). 

In present report we developed new approaches to the synthesis of C- and B-organylsubstituted carboranes using both metallation and cross-coupling reactions, that are of doubtless interest for investigations in the field of Boron Neutron Capture... 

Experimental approaches have been reported by two groups. The group at Gunma University (25) synthesized a prototype of ladder polymers, poly(bicyclosilane)s. Polymers with three, four, and five ladder steps were synthesized, and the bathochromic shifts were measured, Ikehata et al, (26) attempted substitutional doping by thermal neutron irradiation of (SiH) ladder polymers synthesized through the reduction of trichlorosilane with lithium in THE (tetrahydrofuran). Thermal neutron capture by Si will yield P in this process for total flux amounts of up to 10 /cm. The concentration of phosphorus impurity is 0.1 ppm. No serious deterioration was caused by strong neutron irradiation. However, in this study, the detailed properties... 

The formation of most of the heavy elements occurs in one of two processes of neutron capture the s-process or the r-process. These two broad divisions are distinguished on the basis of the relative lifetimes for neutron captures (Xn) and electron decays (t ). The condition that t > where Tp is a characteristic lifetime for /3-unstable nuclei near the valley of /3-stability, ensures that as captures proceed the neutron-capture path will itself remain close to the valley of /3-stability. This defines the s-process. In contrast, when it follows that successive neutron captures will proceed into the neutron-rich regions off the /3-stable valley. Following the exhaustion of the neutron flux, the capture products approach the position of the valley of /3-stability by /3-decay, forming the r-process nuclei. The s-process and r-process patterns in solar system matter are those shown in Figure 2. 

The third means of radionuclide production involves target irradiation by ions accelerated in a cyclotron. One example of this approach is provided by the production of Ge, which decays with a 280 day half-life to the positron emitter Ga. Proton irradiation of Ga produces Ge in a (p,2n) reaction. After dissolution of the target material a solution of the Ge product in concentrated HCl is prepared and adsorbed on an alumina column which has been pre-equilibrated with 0.005 M EDTA (ethylenediaminetetraacetate) solution. The Ga daughter may then be eluted using an EDTA solution in a system which provides the basis of a Ga generator. Cyclotron production of radionuclides is expensive compared with reactor irradiations, but higher specific activities are possible than with the neutron capture process. Also, radionuclides with particularly useful properties, and which cannot be obtained from a reactor, may be prepared by cyclotron irradiation. In one example, cyclotron produced Fe, a positron emitter, may be used for bone marrow imaging while reactor produced Fe, a /3-emitter, is unsuitable. " ... 

Hill et al. were the first to report an interesting approach to combine PDT with boron neutron capture therapy (BNCT) and later studied the selective tumor uptake of a boronated protoporphyrin 6 in mice bearing an implanted intracerebral glioma. TTiey found this compound to be selectively localized in tumor at ratios as high as 400 1 relative to normal brain, indicating that this compound may be used as a potential drug for PDT and boron neutron capture therapy (BNCT). Another approach to overcoming the problem of HpD s chemically complex nature was the use of pure porphyrins such as isohematoporphyrin 7 and... 

It has recently been shown that carbanions generated from carboranes are able to substitute hydrogen in pyrazines, triazine-iV-oxides, and other )t-deficient systems. This original approach to incorporate boron-containing fragments into heterocyclic molecules proved to be rather effective for the s3tnthesis of new ligands and also compounds which can be used for neutron-capture therapy of cancer (Scheme 43) [82, 83]. 

An ingenious approach to this problem is called boron neutron capture therapy (BNCT). This technique brings together two components, each of which separately has minimal harmful effects on the cells. The first component uses a compound containing a stable boron isotope ( °B) that can be concentrated in tumor cells. The second component is a beam of low-energy neutrons. Upon capturing a neutron, the following nuclear reaction takes place ... 

Another situation occurs as a result of an (n,y) reaction, in which an intermediate radionuclide decays to the product of interest. This route is followed to make for example, with the Xe(n, y) Xe process. The neutron capture product Xe beta decays to with a 16.9 h half-life. Because the final product can be chemically separated from the target, specific activity may approach the theoretical value for the pure radionuclide. Obviously, the use of high chemical purity targets and processing reagents is necessary to avoid introducing stable nuclides of the same element as the product. In the example, this means that both the... 

An alternative approach explored functionalization of SWNT with substituted car-borane cages to develop a new delivery system for an efficient boron neutron capture therapy [54]. Indeed, these studies showed that some specific tissues contained carbor-ane following intravenous administration of the CNT conjugate and, more interestingly, that carborane was concentrated mainly at the tumor site. 

---