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PubMedDate not supplied

Synthesis and characterization of oligomeric nido-carboranyl phosphate diester conjugates to antibody and antibody fragments for potential use in boron neutron capture therapy of solid tumors.

Antibodies conjugated to oligomeric carboranyl compounds have a high potential as target species for boron neutron capture therapy (BNCT) of solid tumors. As a first step toward developing conjugates with BNCT capabilities, an oligomeric nido-carboranyl phosphate diester (Kane, R. R., Dreschel, K., and Hawthorne, M.F. (1993) J. Am. Chem. Soc. 115, 8853-8854), CB10 (10 nido-carboranes containing 90 boron atoms) with a pseudo-5'-terminal amino group, was conjugated to the anticarcinoembryonic antigen antibody T84.66 and its F(ab') fragment. The homobifunctional linker disuccinimidyl suberate (DSS) was coupled to CB10 via its 5'-terminal amino group followed by removal of excess linker with organic solvent extraction and conjugation with intact antibody. Similarly, the heterobifunctional linker, m-maleimidobenzoyl-N-hydroxysuccinimide (MBS), was coupled to CB10 and conjugated to the hinge region sulfhydryl of the F(ab') fragment of T84.66. The extent of reaction was monitored by the mobility shift of CB10-antibody conjugate on native polyacrylamide gels and the increased susceptibility of the CB10-antibody conjugate to staining with silver nitrate. CB10 was also labeled with radioiodine (131I) in a solid phase reaction with iodogen and used in double-label studies with 125I-labeled antibody. Although free CB10 bound very tightly to gel filtration media such as Sephadex G-25, the CB10-antibody conjugate passed through freely. After separation of CB10-antibody conjugate from free CB10 on Sephadex G-25, molar incorporations of CB10 were calculated. At a molar ratio of 10:1 (CB10:T84.66), greater than 90% of T84.66 and 30% of its F(ab)' fragment were conjugated to CB10.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

In-phantom imaging of all dose components in boron neutron capture therapy by means of gel dosimeters.

The experimental method for in-phantom imaging and profiling the absorbed dose in neutron capture therapy has been improved. The method separates the contributions of the various secondary radiation components and is based on suitably designed gel dosimeters in the form of layers. The discrimination of the dose components is achieved by means of pixel-to-pixel manipulations of images obtained with gel dosimeters having different isotopic composition. Large dose images are obtainable with this method, because the layer geometry of dosimeters avoids sensible variation of neutron transport due to the isotopic composition of gel. Operation modalities aimed at attaining more reliable results have been studied. Some results, together with the results of punctual measurements performed with conventional dosimeters and with MC calculations, are here reported.

Boron Neutron Capture Therapy↗
PubMed2002

In-phantom two-dimensional thermal neutron distribution for intraoperative boron neutron capture therapy of brain tumours.

The aim of this study was to determine the in-phantom thermal neutron distribution derived from neutron beams for intraoperative boron neutron capture therapy (IOBNCT). Gold activation wires arranged in a cylindrical water phantom with (void-in-phantom) or without (standard phantom) a cylinder styrene form placed inside were irradiated by using the epithermal beam (ENB) and the mixed thermal-epithermal beam (TNB-1) at the Japan Research Reactor No 4. With ENB, we observed a flattened distribution of thermal neutron flux and a significantly enhanced thermal flux delivery at a depth compared with the results of using TNB-1. The thermal neutron distribution derived from both the ENB and TNB-1 was significantly improved in the void-in-phantom, and a double high dose area was formed lateral to the void. The flattened distribution in the circumference of the void was observed with the combination of ENB and the void-in-phantom. The measurement data suggest that the ENB may provide a clinical advantage in the form of an enhanced and flattened dose delivery to the marginal tissue of a post-operative cavity in which a residual and/or microscopically infiltrating tumour often occurs. The combination of the epithermal neutron beam and IOBNCT will improve the clinical results of BNCT for brain tumours.

Boron Neutron Capture Therapy↗
PubMed2006

Effects of boron neutron capture therapy on human oral squamous cell carcinoma in a nude mouse model.

PURPOSE: The effect of boronophenylalanine (BPA)-mediated boron neutron capture therapy (BNCT) on human oral squamous cell carcinoma (SCC) xenografts in nude mice was examined. MATERIALS AND METHODS: Tumor-bearing mice were given BPA at a dose of 250 mg/kg body weight. The tumor (10)B concentration 2 h after an injection of BPA was higher than those 1 or 3 h after the injection. Neutron irradiation was performed beginning 1, 2 or 3 h after an injection of BPA and the effects on body weight of the animals, tumor growth, survival of tumor-bearing animals, and histology of tumor and normal tissue were examined. Fragmented nuclear DNA, 5-bromo-2'-deoxyuridine (BrdU), and von Willebrand Factor (vWF) were detected by immunohistochemical staining. RESULTS: Tumor volumes of untreated control animals increased continuously, whereas those of BNCT-treated animals were markedly decreased. Animals given neutron irradiation 2 h after the injection of BPA survived for a longer period as compared with those given neutron irradiation 1 or 3 h after the injection. BNCT reduced the incorporation of BrdU into tumor cells, and induced the enlargement and vacuolation of tumor cells. Disintegration of blood vessels and dense inflammatory cell infiltration were also observed in the stroma of the tumor, but not surrounding normal tissues. CONCLUSION: These results indicate that BPA-mediated BNCT can exert a curative effect on human oral SCC xenografts in nude mice, if an optimal 10B concentration in tumors is achieved and that the disintegration of blood vessels in tumor stroma may contribute to tumor remission by BNCT.

Animals↗
PubMedDate not supplied

Biodistribution of boron compounds in an animal model of human undifferentiated thyroid cancer for boron neutron capture therapy.

Undifferentiated thyroid carcinoma (UTC) is a rapidly growing, highly invasive malignant tumor that currently lacks any effective treatment. Boron neutron capture therapy (BNCT) has been investigated recently for some types of tumors including glioblastoma multiforme and malignant melanoma. In previous studies we have shown the selective uptake of p-boronophenylalanine (BPA) by undifferentiated thyroid cancer cells in vitro and in vivo, as well as the histologic cure of 50% of the nude mice transplanted with human UTC cells when treated with BPA and an appropriate neutron beam. The present studies were performed to further optimize this treatment through the investigation of a boronated porphyrin, both alone and in combination with BPA. In vitro studies with cells in culture showed that BOPP (tetrakis-carborane carboxylate ester of 2,4-bis-(alpha,beta-dihydroxyethyl)-deutero-porphyrin IX) is localized intracellularly, with a highest concentration in the 11500g (mitochondrial-enriched pellet) fraction. When BOPP was administered alone to NIH nude mice transplanted with UTC human cells, no significant tumor uptake or selectivity in our in vivo model was observed. In contrast, when BOPP was injected 5-7 days before BPA and the animals were sacrificed 60 min after administration of BPA, a significant increase in boron uptake by the tumor was found (38-45 ppm with both compounds vs 20 ppm with BPA alone). On day 5 the tissue boron selectivity ratios were tumor/blood approximately 3.8 and tumor/distal skin approximately 1.8. Other important ratios were tumor/thyroid approximately 6.6 and tumor/lung approximately 2.9. These results open the possibility of improving the efficacy of BNCT for the treatment of this so far "orphan" tumor.

Animals↗
PubMed2006

Therapeutic success of boron neutron capture therapy (BNCT) mediated by a chemically non-selective boron agent in an experimental model of oral cancer: a new paradigm in BNCT radiobiology.

The hypothesis of boron neutron capture therapy (BNCT) research has been that the short-range, high-linear energy transfer radiation produced by the capture of thermal neutrons by (10)B will potentially control tumor and spare normal tissue only if the boron compound selectively targets tumor tissue within the treatment volume. In a previous in vivo study of low-dose BNCT mediated by GB-10 (Na(2)(10)B(10)H(10)) alone or combined with boronophenylalanine (BPA) in the hamster cheek pouch oral cancer model that was primarily designed to evaluate safety and feasibility, we showed therapeutic effects but no associated normal tissue radiotoxicity. In the present study, we evaluated the response of tumor, precancerous and normal tissue to high-dose BNCT mediated by GB-10 alone or combined with BPA. Despite the fact that GB-10 does not target hamster cheek pouch tumors selectively, GB-10-BNCT induced a 70% overall tumor response with no damage to normal tissue. (GB-10+BPA)-BNCT induced a 93% overall tumor response with no normal tissue radiotoxicity. Light microscope analysis showed that GB-10-BNCT selectively damages tumor blood vessels, sparing precancerous and normal tissue vessels. In this case, selective tumor lethality would thus result from selective blood vessel damage rather than from selective uptake of the boron compound.

Animals↗
PubMedDate not supplied

Accelerator-based epithermal neutron sources for boron neutron capture therapy of brain tumors.

This paper reviews the development of low-energy light ion accelerator-based neutron sources (ABNSs) for the treatment of brain tumors through an intact scalp and skull using boron neutron capture therapy (BNCT). A major advantage of an ABNS for BNCT over reactor-based neutron sources is the potential for siting within a hospital. Consequently, light-ion accelerators that are injectors to larger machines in high-energy physics facilities are not considered. An ABNS for BNCT is composed of: (1) the accelerator hardware for producing a high current charged particle beam, (2) an appropriate neutron-producing target and target heat removal system (HRS), and (3) a moderator/reflector assembly to render the flux energy spectrum of neutrons produced in the target suitable for patient irradiation. As a consequence of the efforts of researchers throughout the world, progress has been made on the design, manufacture, and testing of these three major components. Although an ABNS facility has not yet been built that has optimally assembled these three components, the feasibility of clinically useful ABNSs has been clearly established. Both electrostatic and radio frequency linear accelerators of reasonable cost (approximately 1.5 M dollars) appear to be capable of producing charged particle beams, with combinations of accelerated particle energy (a few MeV) and beam currents (approximately 10 mA) that are suitable for a hospital-based ABNS for BNCT. The specific accelerator performance requirements depend upon the charged particle reaction by which neutrons are produced in the target and the clinical requirements for neutron field quality and intensity. The accelerator performance requirements are more demanding for beryllium than for lithium as a target. However, beryllium targets are more easily cooled. The accelerator performance requirements are also more demanding for greater neutron field quality and intensity. Target HRSs that are based on submerged-jet impingement and the use of microchannels have emerged as viable target cooling options. Neutron fields for reactor-based neutron sources provide an obvious basis of comparison for ABNS field quality. This paper compares Monte Carlo calculations of neutron field quality for an ABNS and an idealized standard reactor neutron field (ISRNF). The comparison shows that with lithium as a target, an ABNS can create a neutron field with a field quality that is significantly better (by a factor of approximately 1.2, as judged by the relative biological effectiveness (RBE)-dose that can be delivered to a tumor at a depth of 6cm) than that for the ISRNF. Also, for a beam current of 10 mA, the treatment time is calculated to be reasonable (approximately 30 min) for the boron concentrations that have been assumed.

Beryllium↗
PubMed2006

Recent progress in the syntheses and biological evaluation of boronated porphyrins for boron neutron-capture therapy.

Boronated porphyrins are an important class of tumor-localizing agents in two bimodal therapies for cancer currently under study experimentally and clinically; boron neutron-capture therapy (BNCT) and photodynamic therapy (PDT). The desirable properties for the boronated porphyrins are that they are easily synthesized, pure and well-characterized drugs, and that in vivo, they are stable, tumor-specific, with high tumor:blood and tumor:normal tissue boron concentration ratios, and cause minimal toxicity. A large number of new porphyrins and their syntheses are presented herein. The focus is primarily on porphyrins published within the past 5 years, but the implications and trends from porphyrins studied in vivo over the past 15 years are also reviewed. Many possess quite unusual, novel structures and others have appended cell-targeting moieties for greater tumor specificity. Besides the commonly used closo- and nido-o-carboranes other boron cages and modes of attachment are presented. These boron cages can selectively alter the lipophilic, hydrophilic and amphiphilic properties of the porphyrins as well as their boron content. New delivery modalities have also greatly improved the targeting potential of compounds previously deemed unsuitable for applications in BNCT.

Animals↗
PubMed1994

Radiation effects of boron neutron capture therapy on brain, skin, and eye of rats.

PURPOSE: The present study was carried out to evaluate the radiation effects of boron neutron capture therapy (BNCT) on the brain, skin, and eyes of nude rats following systemic administration of boronophenylalanine (BPA) and neutron irradiation to the head. METHODS AND MATERIALS: A solution containing 120 mg of 10B-enriched-L-BPA complexed with fructose was administered IP to nude rats. Boron concentrations were approximately 8.4, 9.4, 10.0, and 11.0 micrograms/g in the brain, blood, skin, and eyes, respectively, at 6 h when the animals were irradiated at the Brookhaven Medical Research Reactor (BMRR). As determined in a study carried out in parallel with this one, the BNCT radiation doses were sufficient to cause tumor regression in nude rats carrying intracerebral implants of the human melanoma cell line MRA 27. RESULTS: Mild to moderate increases in loose fibrous tissue were observed in the choroid plexus at estimated physical doses to the brain and blood that ranged from 4.3-7.1 Gy and 4.6-7.7 Gy, respectively, and these appeared to be dose and time dependent. Other changes in the choroid plexus included occasional infiltrates of macrophages and polymorphonuclear leukocytes and vacuolation of epithelial cells. Dose-dependent moist desquamation of the skin was observed in all rats, but this had healed by 28 days following irradiation. Cataracts and keratitis developed in the eyes of most animals, and these were dose dependent. CONCLUSION: The minimal histopathological changes seen in the brain at doses that were sufficient to eradicate intracerebral melanoma indicates that BNCT has the potential to cure a tumor bearing host without producing the normal brain injury usually associated with conventional external beam radiation therapy. Studies in canines, which currently are in progress, should further define the dose-effect relationships of BNCT on critical neuroanatomic structures within the brain.

Animals↗
PubMed2004

Evaluation of human thymidine kinase 1 substrates as new candidates for boron neutron capture therapy.

Thymidine analogs containing o-carboranylalkyl groups at the 3-position were screened as potential substrates for human thymidine kinase 1 (TK1), an enzyme that is selectively expressed in a variety of rapidly proliferating cells, including tumor cells. On the basis of previous studies, 12 of these were identified as potential delivery agents for boron neutron capture therapy, a therapeutic method used for the treatment of high-grade brain tumors. Compound 4 with a pentylene spacer between the o-carborane cage and the thymidine scaffold and compound 10, which has an additional dihydroxypropyl substituent at the o-carborane cage, were the best substrates for TK1 with kcat/Km values of 27% and 36% relative to that of thymidine, respectively. These compounds showed partial competitive inhibition for thymidine phosphorylation by TK1. Neither compound was a substrate of recombinant human thymidine phosphorylase nor were their respective 5'-monophosphates substrates of 5'-deoxynucleotidase 1, thereby indicating potential in vivo stability. The octanol/water partition coefficient for compound 10 was 2.09, suggesting that it has excellent physiochemical properties for crossing the blood brain barrier and penetrating brain tissue. The in vitro cytotoxic effect of the 12 analogs was moderate to low in mammalian cell cultures with IC50 values between 10 and 160 micromol/L. Compounds 4 and 10 were taken up selectively and retained by the murine fibroblast L929 cell line, in contrast to its TK1-deficient variant. These findings suggest that compound 10 is a promising candidate for selective delivery of boron-10 to malignant cells, and additional in vivo studies are planned to evaluate it for boron neutron capture therapy of brain tumors.

5'-Nucleotidase↗
PubMed1994

Enhanced therapeutic effect on murine melanoma and angiosarcoma cells by boron neutron capture therapy using a boronated metalloporphyrin.

We have already achieved successful treatment of several human patients with malignant melanoma by boron neutron capture therapy (BNCT) using 10B1-paraboronophenylalanine (10B1-BPA). In this communication we used a new compound, a manganese boronated protoporphyrin (Mn-10BOPP), and compared it to 10B1-BPA.HCl with respect to uptake in murine melanoma and angiosarcoma cells as well as to their respective cell killing effects using BNCT. Mn-10BOPP was found to be 3 to 10 times more effectively taken up by melanoma cells and angiosarcoma cells than 10B1-BPA.HCl when the content of 10B was measured by the new method, inductively coupled plasma-mass spectrometry (ICP-MS). In addition, melanoma cells and angiosarcoma cells preincubated with Mn-10BOPP were 15 to 20 times more efficiently killed by BNCT than cells preincubated with 10B1-BPA.HCl. These results suggest that Mn-10BOPP is a suitable compound for BNCT of not only malignant melanoma but also angiosarcoma.

Animals↗
PubMed1994

Strategies for the design and synthesis of boronated nucleic acid and protein components as potential delivery agents for neutron capture therapy.

PURPOSE: Strategies for the design and synthesis of boronated nucleosides, amino acids, and peptides as potential delivery agents for boron neutron capture therapy (BNCT) are described. METHODS AND MATERIALS: For BNCT to be a useful treatment modality, there is a need to design and synthesize nontoxic boron compounds that selectively target tumor cells, accumulate in sufficient amounts (20-30 micrograms 10B/g of tumor) and persist at therapeutic levels for a sufficient time prior to neutron irradiation. Boronated nucleosides, amino acids and peptides are such promising target compounds. Such structures may be selectively used by proliferating neoplastic cells compared with mitotically less active normal cells and therefore achieve the tissue differentials necessary for BNCT. RESULTS: The rationale for synthesis of boronated nucleic acid and protein components is discussed. Results of biological and clinical studies of some boronated nucleosides, nucleotides, amino acids and peptides are presented. CONCLUSION: Boronated nucleosides, amino acids and peptides can be considered as potential targeting agents for BNCT.

Boron Compounds↗
PubMed1996

Enhanced delivery of boronophenylalanine for neutron capture therapy by means of intracarotid injection and blood-brain barrier disruption.

There has been increasing interest in the possible use of boronophenylalanine as a capture agent for boron neutron capture therapy of brain tumors. The purpose of the present study was to determine whether the uptake of boronophenylalanine in F98 glioma-bearing rats could be enhanced by means of intracarotid (i.c.) injection with or without blood-brain barrier disruption (BBB-D). Glioma cells (10(5)) were stereotactically implanted into the right cerebral hemisphere of Fischer rats, and 12 days later, BBB-D was performed by infusing 25% mannitol (1.373 mOsmol/ml) into the right carotid artery and then immediately injecting L-boronophenylalanine (300 mg/kg of body weight) intracarotidly. The animals were killed 0.5, 1, 2.5, and 4 hours later, and the brains were removed for boron determination by direct current plasma atomic emission spectroscopy. BBB-D was assessed by the intravenous injection of Evans blue or horseradish peroxidase, and the barrier-disrupted hemispheres and tumors showed intense staining with each. The mean tumor boron concentration after i.c. injection and BBB-D was 34.8 +/- 6.8 micrograms/g at 2.5 hours compared with 20.3 +/- 6.2 micrograms/g after i.c. injection without BBB-D and 10.7 +/- 0.7 micrograms/g after intravenous injection. No significant differences in boron concentration in muscle, skin, and eye were observed among the different groups. Boron concentrations in the ipsilateral, disrupted hemisphere increased transiently but rapidly returned to background levels by 2.5 hours after BBB-D. The tumor:brain and tumor:blood ratios were 5.2 and 5.6, respectively, compared to 3.2 and 2.1 for intravenous injection groups at 2.5 hours. The present study is the first to show that BBB-D combined with i.c. injection can enhance the tumor uptake of boron compounds for boron neutron capture therapy.

Animals↗
PubMed2000

Phantom materials for boron neutron capture therapy.

The aim of this work was to establish which reference phantom material is most suited for dosimetry under reference conditions of neutron beams for boron neutron capture therapy (BNCT). For this purpose, phantoms of dimensions 15 x 15 x 15 cm3 and 30 x 30 x 30 cm3, composed of water, tissue-equivalent (TE) liquid, polyethylene (PE), polymethyl methacrylate (PMMA) and water containing 10 microg g(-1) and 30 microg g(-1) 10B were irradiated using the Petten BNCT beam. Activation foils and a diode detector were used for the determination of the thermal neutron fluence rate. The gamma-ray dose rate and the fast neutron dose rate were determined using paired ionization chambers. In water, PMMA and TE liquid the absolute dose and fluence values agreed within 3% at a reference depth of 2 cm, with the exception of the gamma-ray dose rate in PMMA, which was 12% lower than in water. Due to a higher hydrogen concentration in PE compared with water, the dose and fluence values in PE differed more than 30% from those in water. Only minor differences were observed between the percentage depth dose curves for the various dose components in water, PMMA and TE liquid. The addition of 10 microg g(-1) and 30 microg g(-1) 10B to water resulted in a decrease in the absolute thermal neutron fluence at 2 cm depth of about 2% and 8%, respectively, and a decreased penetration of thermal neutrons at depth for the 30 microg g(-1) 10B concentration. For reference dosimetry of an epithermal neutron beam for BNCT, both water and TE liquid are suitable phantom materials. For practical reasons, water is therefore proposed as reference phantom material. For measurements requiring a solid phantom, PMMA is proposed. The lower gamma-ray dose in PMMA compared to water, however, needs to be taken into account.

Boron↗
PubMed1989

Ultrastructural microvascular response to boron neutron capture therapy in an experimental model.

A CD 344 rat glioma model currently used to investigate boron neutron capture therapy (BNCT) was used to demonstrate an increased survival rate after thermal neutron irradiation enhanced by administration of 10B-enriched polyhedral borane, Na2B12H11SH. To investigate the possible effects of BNCT on normal and tumor microvasculature, we subjected animals to sublethal neutron irradiation with and without intravenous injection of 50 mg/kg of enriched 10B and performed histological and ultrastructural analyses. In the rats that did not undergo tumor transplantation, minimal detectable morphological changes in the microvasculature of the central nervous system were observed after treatment, both in the immediate posttreatment phase and at 10 months. Light microscopy of cerebral cortex and caudate nucleus showed normal cytoarchitecture with no evidence of vessel occlusion, hyalinization, thickening, or reactive gliosis. Electron microscopy demonstrated that the junctional complexes of the endothelial cells, the basal lamina, and the perivascular glia were comparable in both treated and control animals. In those animals examined at 18 months, pathological membrane-bound clusters of electron-dense vesicles were seen in pericytes. In the rats implanted with gliomas, vascular proliferation with evidence of breakdown of the blood-brain barrier and vasogenic edema occurred. In the irradiated animals, we noted increased peritumoral edema 3 days after treatment. At seven days, both increased peritumoral edema and necrosis were noted in the rats treated with BNCT. These observations show that the normal microvasculature of the central nervous system tolerates BNCT at the treatment parameters used in our experimental model; the progressive edema and necrosis found in the peritumoral region after BNCT indicate a pathological endothelial response.

Animals↗
PubMed2006

Feasibility of boron neutron capture therapy (BNCT) for malignant pleural mesothelioma from a viewpoint of dose distribution analysis.

PURPOSE: To investigate the feasibility of boron neutron capture therapy (BNCT) for malignant pleural mesothelioma (MPM) from a viewpoint of dose distribution analysis using Simulation Environment for Radiotherapy Applications (SERA), a currently available BNCT treatment planning system. METHODS AND MATERIALS: The BNCT treatment plans were constructed for 3 patients with MPM using the SERA system, with 2 opposed anterior-posterior beams. The (10)B concentrations in the tumor and normal lung in this study were assumed to be 84 and 24 ppm, respectively, and were derived from data observed in clinical trials. The maximum, mean, and minimum doses to the tumors and the normal lung were assessed for each plan. The doses delivered to 5% and 95% of the tumor volume, D(05) and D(95), were adopted as the representative dose for the maximum and minimum dose, respectively. RESULTS: When the D(05) to the normal ipsilateral lung was 5 Gy-Eq, the D(95) and mean doses delivered to the normal lung were 2.2-3.6 and 3.5-4.2 Gy-Eq, respectively. The mean doses delivered to the tumors were 22.4-27.2 Gy-Eq. The D(05) and D(95) doses to the tumors were 9.6-15.0 and 31.5-39.5 Gy-Eq, respectively. CONCLUSIONS: From a viewpoint of the dose-distribution analysis, BNCT has the possibility to be a promising treatment for MPM patients who are inoperable because of age and other medical illnesses.

Boron Compounds↗
PubMed2006

Characterization of moderator assembly dimension for accelerator boron neutron capture therapy of brain tumors using 7Li(p, n) neutrons at proton energy of 2.5 MeV.

The characteristics of moderator assembly dimension are investigated for the usage of 7Li(p,n) neutrons by 2.5 MeV protons in boron newtron capture therapy (BNCT) of brain tumors in the present study. The indexes checked are treatable protocol depth (TPD), which is the greatest depth of the region satisfying the dose requirements in BNCT protocol, proton current necessary to complete BNCT by 1 h irradiation, and the heat flux deposited in the Li target which should be removed. Assumed materials are D2O for moderator, and mixture of polyethylene and LiF with 50 wt % for collimator. Dose distributions have been computed with MCNP 4B and 4C codes. Consequently, realized TPD does not show a monotonical tendency for the Li target diameter. However, the necessary proton current and heat flux in the Li target decreases as the Li target diameter increases, while this trend reverses at around 10 cm of the Li target diameter for the necessary proton current in the condition of this study. As to the moderator diameter, TPD does not exhibit an apparent dependence. On the other hand, necessary proton current and heat flux decrease as the moderator diameter increases, and this tendency saturates at around 60 cm of the moderator diameter in this study. As to the collimator, increase in inner diameter is suitable from the viewpoint of increasing TPD and decreasing necessary proton current and heat flux, while these indexes do not show apparent difference for collimator inner diameters over 14 cm for the parameters treated here. The practical viewpoint in selecting the parameters of moderator assembly dimension is to increase TPD, within the technically possible condition of accelerated proton current and heat removal from the Li target. In this process, the values for which the resultant characteristics mentioned above saturate or reverse would be important factors.

Boron Neutron Capture Therapy↗
PubMed1992

Local control of subcutaneous murine melanoma xenografts in nude mice by neutron capture therapy.

The systemic administration of enriched [10B]D,L-p-boronophenylalanine results in the selective uptake of boron by Harding-Passey melanoma xenografts in the nude mouse model. The boron-10 located in the tumour cells acts as a radiation sensitizer for thermal neutron irradiation. The nude mouse model can be successfully used to demonstrate that regression and local control of melanoma can be achieved by neutron capture therapy. Control is a manifestation of the high linear energy transfer radiation released after neutron capture by boron-10, and does not result from an equal fluence of neutrons alone. Histological examination of remnant tumour beds 300 days after treatment shows the presence of isolated melanoma cells. However, these cells are few in number and appear incapable of division.

Animals↗