Boron neutron capture therapy tumor treatment

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). 

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... 

Use of dendrimers such as PAMAM, PPI and poly(ether hydro q lamine) (PEHAM) in drug deliveiy is mostly focused on cancer treatment. Dendrimers encapsulate anticancer drugs such as cisplatin and doxorubicin and agents for boron neutron capture therapy and photodynamic therapy. Cisplatin encapsulated dendrimers are reported to increase the bioavailability and selectivity of the drug on a solid tumor model which was provided by injection of B16F10 cells to C57 mice. ... 

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. 

By itself not particularly strong or durable, aluminum in combination with other metals becomes one of the most versatile materials available. It does take vast amounts of electrical energy to manufacture, however, and presently this involves the production of both carbon dioxide and the sulfur oxides. Alums are astringents and the sources of beautiful crystals. Alumina, the oxide, comes in a variety of polymorphs used as various abrasives and in beautiful, gem-quality minerals. It is also the product of the extremely exothermic thermite reaction. Boron Neutron Capture Therapy (BNCT) offers a potential treatment against brain tumors and other difficult-to-treat carcinomas of the head and neck. Gallium, indium, and thallium compounds do not have many applications. 

FIGURE 2.4 Examples of bisphosphonic acid derivatives of ort/jo-carborane reported in the patent literature. (Adapted from Benedict, J. J. EP 0068584 Al, 1981. Boron-containing polyphosphonates for the treatment of calcific tumors Komagata, T., Kawanabe, T., Matsushita, T. Jpn Kokai Tokyo Koho, JP 11-080177, A2, Heisei, 1999. Preparation of boron-containing bisphosphonic acids as agents for boron neutron capture therapy.)... 

Boron neutron capture therapy (BNCT) is one of the most promising methods for cancer treatments. This binary method involves selective introduction of B-10 containing compounds to tumor cells, followed by irradiation with thermal neutrons. BNCT is focused mainly on the treatment of malignant brain tumors, for example, glioblastoma multiforme, which is virtually untreatable via surgery. Two recent publications by Ciofani et al. described BNNTs as a drug carrier for BNCT. ... 

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]. 

Yamamoto has reported the synthesis of (4-boronylphenyl)alanine (BPA), used dinically for treatment of malignant melanoma and brain tumors in neutron capture therapy by Pd-catalyzed coupling of triflate 47 with the diboron derivative 48 [22]. The boronic ester 49 could be easily cleaved by hydrogenolysis to give I-BPA 50 in 74% yield, whereas the corresponding pinacol ester yielded mixture... 

In contrast to many chemotherapeutic agents in cancer therapy, boron compounds for BNCT do not require a tumoricidal action in their own right. For their successful application in the therapy of patients, it is important to deliver, to the tumor, a radiation dose which is higher than the radiation dose to the surrounding tissue. The demonstration that this is actually achieved lies ultimately in the treatment of the tumor in question. Because of the short range of the particles produced in the 10B(n,a)7Li reaction, it is very important where, on a cellular and subcellular dimension, the neutron capture reaction takes place. Different methods for boron detection and quantification give different resolution of the boron distribution. It is instructive to compare these methods, both for their precision and lower detection limits, as well as for their ability to yield an image of the boron distribution in tissue (Table 2.2-1). 

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