Ebook: Advances in Neutron Capture Therapy

Binary systems for the treatment of cancer potentially are among the most attractive of the new therapeutic modalities that currently are under investigation. The basicconcept is to selectivelydestroy malignantcells whileconcomitantlysparing normal tissue. Neutron capture therapy (NCT) is the binary system that has been the subject of the Fifth International Symposium on Neutron Capture Therapy, which was held September13-17, 1992, in Columbus, Ohio, undertheauspicesoftheInternational Society for Neutron Capture Therapy. Its objective was to bring together researchers from throughout the world and to provide a forum at which they could present the latest advances in the development of Neutron capture therapy. Neutron capture therapy has largely, but not exclusively, focused on the use of boron-10 as the target nuclide. Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when the stable isotope, boron-10, absorbs low-energy non­ ionizing thermal neutrons to yield alphaparticles and recoiling lithium-7 nuclei. The size and energy of these high linear energy transfer (LET) particles result in their being confined largely to the cells in which the capture reaction occurs. For BNCT to be successful, a sufficient numberof I~atoms mustbe localized within neoplastic cells, and enough thermal neutrons must be delivered and absorbed by the I~ to produce a lethal 1~(n,QVLi reaction. Two major problems must be surmounted.

---

---

Content:
Front Matter....Pages i-xxx
Review of Reactor-Based Neutron Beam Development for Bnct Applications....Pages 1-7
Evaluation of Neutron Irradiation Fields for Bnct by Using Absorbed Dose in a Phantom....Pages 9-13
Analysis of Filtered Neutron Beams At Hifar....Pages 15-20
Filtered Neutron Beam Measurements at Hifar....Pages 21-24
Preclinical Tests for Neutron Capture Therapy on the Lvr-15 Reactor....Pages 25-28
Study on Remodeling the Heavy Water Facility of the Kyoto University Reactor for Neutron Capture Therapy from the Concept of Neutron Energy Spectrum Control....Pages 29-32
Improvement of Thermal Neutron Fluence for Bnct Treatment of Deep—Seated Tumors: Simulation Calculation and Phantom Experiments....Pages 33-36
The Sensitivity of Research Reactor Based Bnct Irradiation Facility Performance to Core Conversion from High to Low Enriched Uranium Fuels....Pages 37-41
Neutron Spectrum Determination for the Boron Neutron Capture Therapy Program in Thailand....Pages 43-46
A Standardized Method for Beam Design in Neutron Capture Therapy....Pages 47-51
Application of Fricke Dosimetry for Bnct....Pages 53-57
Nuclear Characterisation of the Hfr Petten Bnct Facility....Pages 59-65
A Comparison of Epithermal Neutron Beams for Nct: Effect of Beam Collimation on Therapy Parameters....Pages 67-70
Physics Parameters for an Epithermal—Neutron Beam at the Georgia Institute of Technology....Pages 71-74
Enhancement of the Epithermal Neutron Beam at the Brookhaven Medical Research Reactor....Pages 75-79
Epithermal BNCT Neutron Beam Design for a Triga II Reactor....Pages 81-84
Generating Epithermal Neutron Beams for Neutron Capture Therapy in Small Reactors....Pages 85-88
Epithermal and Fast Neutron Spectrum Measurement at the Brookhaven Medical Research Reactor (Bmrr)....Pages 89-93
Accelerator-Based Epithermal Neutron Beams for Neutron Capture Therapy....Pages 95-98
Effect of Variations in the RBE on the Design of an AENIF for BNCT....Pages 99-103
Low Energy Accelerator-Based Neutron Sources for Neutron Capture Therapy....Pages 105-108
An Epithermal Neutron Beam from the MURR and from an Accelerator Source Compared to the Beam at the BMRR....Pages 109-113
Monte Carlo Shielding Analysis for an Accelerator Epithermal Neutron Irradiation Facility (AENIF) in a Conventional X-Ray Irradiation Room....Pages 115-118
Accelerator Neutron Irradiation Facility for Hospital-Based Neutron Capture Therapy....Pages 119-123
On the Study of Energy Spectra and Angular Distributions of the Neutrons Emitted from a Beryllium Target Bombarded with 4-MeV Protons for Neutron Capture Therapy....Pages 125-129
Californium-Based Epithermal Neutron Beams for Neutron Capture Therapy....Pages 131-134
Cf-252 Neutrons for the Treatment of Superficial Carcinomas....Pages 135-137
Cf-252 Neutron Therapy and Neutron Capture Therapy....Pages 139-141
Analytical Dosimetry and Treatment Planning for BNCT....Pages 143-146
Potential MCNP Enhancements for NCT....Pages 147-151
Post Treatment Dose Distribution Evaluation for a Recent NCT Patient....Pages 153-157
Measurements and Calculations for Boron Neutron Capture Therapy Treatment Planning....Pages 159-163
Dose Calculation and Treatment Planning for the Brookhaven NCT Facility....Pages 165-169
SBNCT Plan: A 3-Dimensional Treatment Planning System for Boron Neutron Capture Therapy....Pages 171-175
Removal-Diffusion Theory for Calculation of Neutron Distributions in BNCT....Pages 177-180
Possibility of Application of Acoustic Pulse Generation to Dose Distribution Monitoring during Neutron Capture Therapy....Pages 181-183
Refinements of Monte Carlo Calculations for BNCT at the Brookhaven Medical Reactor....Pages 185-189
The Effect of Incident Neutron Energy and Tumor Depth in BNCT Study....Pages 191-195
Modified Advantage Depth and Maximum Therapeutic Depth in Thermal Neutron Capture Therapy....Pages 197-200
Biological Effectiveness of Recoil Protons from Neutrons of Energy 5 keV to 5 MeV....Pages 201-205
On the Development of a Scintillation Spectrometer for Comparison of Neutron Energy Spectra at High and Low Flux....Pages 207-211
Microdosimetry and Compound Factors for Neutron Capture Therapy....Pages 213-216
Analytical Dose Calculation in Cell Nucleus from Spherical 10B Containing Region and a Concept of RBE for Neutron Capture Therapy....Pages 217-220
Monte Carlo Calculation of Microdosimetry in Nitrogen and Boron Neutron Capture Reactions....Pages 221-224
Gadolinium as an Element for Neutron Capture Therapy....Pages 225-229
Monte Carlo Dose Distribution of Gadolinium NCT for Brain Tumors of Different Site and Level of Necrosis....Pages 231-234
Evaluation of Depth-Dose Distributions for Gadolinium Neutron Capture Therapy....Pages 235-239
Gadolinium Neutron Capture Therapy: Growth Suppression of Ehrlich Ascites and Subcutaneously-Implanted Tumor Cells in Mice....Pages 241-243
Biological Dosimetry for Gadolinium Neutron Capture Reaction....Pages 245-248
Capture of p-Boronophenylalanine by Melanin-Related Compounds: Complex Formation of p-Boronophenylalanine with L-Dopa....Pages 249-252
Proposed Mechanism of Capture and Release of p-Boronophenylalanine in Melanoma Cells: Chemical Behavior of p-Boronophenylalanine-Fructose Complex in L-Dopa Solution....Pages 253-256
Relation between Structures of p-Boronopiienylalanine Related Compounds and Their Usefulness for Boron Neutron Capture Therapy....Pages 257-260
Synthesis of o- and m-Boronophenylalanine....Pages 261-264
Synthesis of Carboranylphenylalanine for Potential Use in Neutron Capture Therapy....Pages 265-268
Asymmetric Synthesis of Carboranyl Amino Acids with Potential Use in BNCT....Pages 269-272
Novel Carboranyl Amino Acids and Peptides....Pages 273-276
Enantioselective Synthesis of an Unnatural Amino Acid, L-Carboranylalanine....Pages 277-280
Synthesis and Evaluation of Carborane-Containing Amino Acids for Boron Neutron Capture Therapy....Pages 281-284
Synthesis, Antiviral Activity, Cytotoxicity, and Cellular Pharmacology of 5-Carboranyl-Pyrimidine Nucleosides....Pages 285-288
Synthesis of Carborane-Containing Nucleosides, Nucleotides, and Carbohydrates for Bnct....Pages 289-292
Novel Carboranyl Diols and Their Derived Phosphate Esters....Pages 293-296
Ether Lipids as Potential Boron Carriers for Boron Neutron Capture Therapy: Synthesis of rac-1-(9-o-Carboranyl)nonyl-2-Methyl-Glycero-3-Phosphocholine (B-Et-11-OMe)....Pages 297-300
A Boronated Metalloporphyrin for use in Neutron Capture Therapy and Magnetic Resonance Contrast Enhancement of Glioma....Pages 301-303
Synthesis and Biological Properties of Carboranylaziridine....Pages 305-308
Preparation of Meta -Carboranylpropyl-2-Nitroimidazole Derivatives for Application to BNCT....Pages 309-313
Hypoxia-Selective Cellular Toxicity of Carboranyl-Nitroimidazole....Pages 315-318
Preparation of Meta-Carborane Derivatives by Thermal Rearrangement in a Small Scale Laboratory Apparatus.....Pages 319-323
Carbonyl Nonahydrodecaborate(1-): A Versatile Synthon for Functionalized Borane Anions....Pages 325-328
Synthesis of Monocarbon Carboranes with Potential for Application in 10B Neutron Capture Therapy....Pages 329-332
Synthesis and Evaluation of Amine Reactive Carboranyl Derivatives for Application to Boron-10 Containing Polymers....Pages 333-337
Synthesis and Preliminary in Vivo Toxicity Evaluation of an Iodinated Sulfidoborate....Pages 339-343
Boron Delivery to Tumors Mediated by Macromolecules and Vesicles....Pages 345-350
In Vivo Distribution of Boronated Monoclonal Antibodies and Starburst Dendrimers....Pages 351-355
Binding of Boronated Polylysine to Immunoglobulin by Way of Glycoside Moieties: Immunoreactivity and Boron Content....Pages 357-360
Boronated Peptides and Nucleic Acid Components for Nct....Pages 361-365
Targeting of Boronated Anti-Afp MoAB to Hepatoma Cells: Applications of Boronated MoAB for BNCT....Pages 367-370
Epidermal Growth Factor as a Potential Targeting Agent for Delivery of 10B to Malignant Gliomas....Pages 371-375
Evaluation of a10B-Labelled DNA Ligand....Pages 377-381
Synthesis and Evaluation of 157Gd-Labelled DNA Ligands....Pages 383-387
Chemical and Enzymatic Incorporation of Boron into DNA....Pages 389-393
Liposomal Delivery of Boron to Murine Tumors for Boron Neutron Capture Therapy....Pages 395-398
Low Density Lipoprotein Reconstitutions with Alkyl and Aryl Carboranes....Pages 399-402
A Rapid Method for the Direct Analysis of Boron in Whole Blood by Atomic Emission Spectroscopy....Pages 403-407
Quantification of Boron in Biological Tissue by Secondary Ion Mass Spectrometry....Pages 409-412
Ftir Spectrometry for the Assay of Polyhedral Boron Compounds in Plasma....Pages 413-417
Prompt Gamma-Ray Analysis to Determine 10B Concentrations....Pages 419-422
Probing Boronated Nucleoside Utilization by Glioma Cells Using Ion Microscopy....Pages 423-427
Subcellular Localization Study of Boronated Uridine and Glucose Derivatives in Cell Cultures Using Ion Microscopy....Pages 429-433
The Analysis of Boron in Dextran-Sulfhydrylborane Conjugates....Pages 435-438
Determination of Strongly Protein-Bound Borocaptate Species by High Performance Liquid Chromatography with on-Line Inductively Coupled Plasma Atomic Emission Spectroscopy Detection of Boron....Pages 439-443
Optimisation of Neutron Capture Radiography for Analysis of Boron-10 in Tissues....Pages 445-448
The Application of an Alpha Autoradiographic Technique for Determination of Boron-10 Concentrations in a Study of Intratumoral Injection of BSH and CBU-2’....Pages 449-451
NMR Studies of the Interaction of Borocaptate Sodium with Serum Albumin....Pages 453-457
Purity and Quality Determinations of Borocaptate Sodium....Pages 459-463
Determination of p-Boronophenylalanine in Biological Tissues with High Performance Liquid Chromatography....Pages 465-468
Large Animal Studies on the Use of BNCT for the Treatment of Brain Tumors....Pages 469-475
Lessons Learned from Hypoxic Sensitizer and Photodynamic Therapy Research of Potential Use to BNCT....Pages 477-483
RG2 Rat Glioma Model: Influence of the Blood-Brain Barrier on Biodistribution of Boronsulfhydryl....Pages 485-490
Pharmacokinetics and Tissue Distribution of Boronophenylalanine Following Intraperitoneal Injection in Nude Rats with Intracerebral Melanoma....Pages 491-494
Uptake of 10B in Gliosarcomas Following the Injection of Glutathione Monoethyl Ester and Sulfhydryl Borane....Pages 495-499
Biodistribution of a Boronated Porphyrin in BC-1 Mammary Carcinoma....Pages 501-504
Blood-Brain Barrier Permeability in Partially Deuterated Rat Brain....Pages 505-508
Cardiovascular Toxicities Associated with Intravenous Administration of P-Boronophenylalanine Formulations....Pages 509-512
Treatment of Intracerebral Malignant Melanoma Using a Rat Model and L-Boronophenylalanine as the Capture Agent....Pages 513-517
Effects of Fractionation of Boron Neutron Capture Therapy in a Mouse Glioma Model....Pages 519-523
Californium-252 Brachytherapy of Intracerebral Melanoma with and without Administration of Boronophenylalanine Utilizing a Nude Rat Model....Pages 525-528
Boron Neutron Capture Therapy: Skin and Spinal Cord Tolerance....Pages 529-533
An Intra-Pancreatic and Hepatic Nude Mouse Cancer Xenograft Model for Boron Neutron Capture Therapy....Pages 535-539
Boron Neutron Capture Therapy (BNCT) of F98 Glioma Bearing Rats Using Boronophenylalanine (BPA) as a Capture Agent....Pages 541-545
Histological Examination of Murine Melanoma Xenografts in the Nude Mouse Model: Pre and Post Neutron Capture Therapy....Pages 547-550
Evaluation of Dose Components for Healthy Tissue Tolerance Studies on Dogs at the HFR Petten....Pages 551-555
Dose Effect Comparisons between HFR and BMRR Irradiated Dogs with Respect to Healthy Tissue Tolerance....Pages 557-560
Developments in Healthy Tissue Tolerance Studies as a Precondition for Clinical Application of Boron Neutron Capture Therapy....Pages 561-564
Brain Effects Observed in the Canine Healthy Tissue Tolerance Studies for BNCT with Borocaptate Sodium at the Epithermal Neutron Beam of the HFR, Petten....Pages 565-569
Pharmacokinetics of Borocaptate Sodium in Canine Head Determined by 11B Magnetic Resonance Imaging and Spectroscopy....Pages 571-574
Bioavailability of Intravenous Formulations of P-Boronophenylalanine in Dog and Rat....Pages 575-578
Computer Modeling the Boron Compound Factor in Normal Brain Tissue....Pages 579-583
Computer Modeling the Boron Compound Factor in Brain Tumors....Pages 585-589
Determination of Fast—Neutron Dose Distributions in the Canine Central Nervous System....Pages 591-595
Dose Optimization for Boron Neutron Capture Therapy of Spontaneous Canine Brain Tumors....Pages 597-601
Cellular Uptake, Subcellular Distribution and In Vitro Toxicity of Carboranyl Uridines....Pages 603-606
The Use of Boron Neutron Capture for the Treatment of Pituitary Tumors....Pages 607-611
Characteristics of Melanoma Cells Regarding Binding of Carboranylalanine and Effects of Boron Neutron Capture....Pages 613-617
Irradiation of Single Cells with Individual High-Let Particles....Pages 619-622
Thermal Neutron Capture Therapy Using 10B1-Bpa: Inducement of Marked Lethal Effect on Melanoma Cells Irrespective of X-Ray Sensitivity....Pages 623-628
Bibenzimidazoles as Radioprotectors Against Bnc-Induced Dna Damage....Pages 629-632
Rbe: A Useful Concept in Neutron Therapy and Bnct?....Pages 633-638
A Comparison of the Dose-Rbe and the Biological Dosimetry Approaches for Treatment Planning in Bnct....Pages 639-643
A PC-Based Computer Program for the Estimation of the Radiation Dose in in Vitro and in Vivo Boron Neutron Capture Irradiation Experiments....Pages 645-648
New Dimensions of Boron Thermal Neutron Capture Therapy in Neurosurgery....Pages 649-652
Thermal Neutron Capture Therapy for Brain Stem and Skull Base Tumors: Heavy Water and Multiportal Neutron Delivery....Pages 653-657
A Treatment Protocol for Bnct of Malignant Gliomas with Borocaptate Sodium (BSH) and Epithermal Neutrons....Pages 659-663
Experiences of BNCT Using the KUR....Pages 665-669
Clinical Experience with Bnct for Malignant Brain Tumors....Pages 671-675
Current Standard Boron Neutron Capture Therapy with Shionogi’s Mercaptoundecahydrododecaborate for Malignant Glioma....Pages 677-681
Endovascular Boron Neutron Capture Radiotherapy for Giant Arteriovenous Malformations....Pages 683-687
Selective Melanoma Thermal Neutron Capture Therapy for Lymph Node Metastases....Pages 689-693
Deuteriation Trials for Neutron Capture Therapy of Deep-Seated Melanoma Lesions....Pages 695-698
Correlation of Bsh Uptake with CT-Scan Contrast Enhancement in Patients with Intracranial Tumors....Pages 699-703
Update on Biodistribution of Borocaptate Sodium (BSH) in Patients with Intracranial Tumors....Pages 705-710
Results of Continued Clinical Investigations of BSH in Patients with Malignant Glioma....Pages 711-714
The Biodistribution of p-Boronophenylalanine-Fructose in Human Patients with Glioma and Metastatic Melanoma....Pages 715-717
On the Progress Towards Clinical Trials at Petten (Post-Sydney)....Pages 719-726
Designing a Treatment Room for BNCT Clinical Trials at the HFR, Petten....Pages 727-730
Federal and Institutional Approvals Necessary Prior to A U.S. Clinical Trial of Neutron Capture Therapy....Pages 731-733
Preparations for Clinical Trials at the MIT Reactor and the New England Medical Center....Pages 735-738
Procedures for the Medical Application of Research Reactors....Pages 739-743
A Proposal for Low Dose Rate Beam Therapy for Glioblastoma....Pages 745-748
Roundtable Discussion on Neutron Capture Therapy....Pages 749-752
“Summing UP”: The Physics of NCT....Pages 753-756
Compound Development and Analytical Studies....Pages 757-759
Summing UP: Biological Studies Relating to BNCT....Pages 761-768
Summing UP: Clinical Papers....Pages 769-774
Back Matter....Pages 775-779
....Pages 781-787