Cancer Neutron CaptureTherapy

Edited by

Yutaka MishimaMishima Institute for Dermatological ResearchKobe, Japan

Plenum Press • New York and London

CONTENTS

Presidential A ddress

1. Selective Thermal Neutron Capture Therapy of Cancer Cells Using TheirSpecific Metabolic Activities—Melanoma as Prototype

Y. Mishima

Chemistry

Macromolecular Species

2. Recent Results with Liposomes as Boron Delivery Vehicles for Boron NeutronCapture Therapy 27

M. F. Hawthorne, D. A. Feakes, and K. Shelly

3. Preparation of Epidermal Growth Factor Conjugates Aimed for Boron NeutronCapture Therapy 37

L. Gedda, P. Olsson, and J. Carlsson

4. Epidermal Growth Factor (EGF) as a Potential Targeting Agent for Delivery ofBoron to Malignant Gliomas 43

J. Capala, R. F. Barth, D. M. Adams, M. Q. Bailey, A. H. Soloway, andJ. Carlsson

5. Boron Neutron Capture Therapy against Tumor Cells with Overexpression ofthe EGF-Receptor 49

J. Carlsson, L. Gedda, C. Gronvik, T. Hartman, A. Lindstrom,H. Lundqvist, A. Lovqvist, J. Malmqvist, P. Olsson, J. Ponten,S. Sjoberg, A. SjostrSm, B. Stenerlow, N. Tilly, M. Essand, W. Tjarks,and B. Westermark

XV

xvi Contents

6. Boron-Rich Oligophosphates-Novel Molecules for Use in BNCT 57R. R. Kane, K. Drechsel, Y. Soo Kim, C. L. Beno, C. S. Lee, G. Mendez,

S. Romano, and M. F. Hawthorne

7. Potential Use of Bispecific Antibodies (BSABS) for Targeting Gliomas andMelanomas 67

L. Liu, R. F. Barth, D. M. Adams, A. H. Soloway, and R. A. Reisfeld

8. Effect of Intratumoral Injection of IOB-Immunoliposome on BNCT for GrowthInhibition of Human Pancreatic Cancer Grafts in Nude Mice 75

H. Yanagie, T. Tomita, H. Kobayashi, Y. Fujii, Y. Saegusa, M. Eriguchi,T. Kobayashi, K. Kanda, and K. Ono

BPA and other Amino Acids

9. Chemical Modeling with p-Boronophenylalanine for Boron Accumulation toand Release from Melanoma 81

K. Yoshino, Y. Mori, H. Kakihana,H. Takahashi, Y. Mishima, andM. Ichihashi

10. Chemical Properties of/?-, m-, o-Boronophenylalanine 91K. Yoshino, N. Watanabe, H. Takahashi, S. Watanabe, Y. Mori,

M. Ichihashi, H. Kakihana, and Y. Mishima

11. An Efficient Synthesis of p-Boronophenylalanine and Its Homologues by theReaction of Ethyl Isocyanoacetate with a p-Formylbenzeneboronic AcidDerivative 99

M. Kirihata, T. Morimoto, I. Ichimoto, and M. Takagaki

12. New Unnatural Boron-Containing Amino Acids and Peptides as PotentialDelivery Agents for Neutron Capture Therapy 105

I. M. Wyzlic, J. C. Beeson, A. H. Soloway, J. Yong, and R. F. Barth

13. Study of the Interaction ofp-Boronophenylalanine and Its Analogs withVarious Carboxylic Acids by Using Zone Electrophoresis I l l

Y. Kitaoka, M. Kobayashi, K. Kawamoto, T. Morimoto, M. Kirihata, andI. Ichimoto

14. Examination of Stability of/?-, m-, o-Boronophenylalanine in Blood with HighPerformance Liquid Chromatography 115

K. Yoshino, N. Koike, Y. Kuroda, Y. Mori, M. Ichihashi, H. Kakihana, andY. Mishima

15. Synthesis and Initial Biological Evaluation of Carborane-ContainingPhenanthridinium Derivatives 121

W. Tjarks, J. Malmquist, L. Gedda, S. Sjoberg, and J. Carlsson

16. Chemical Behavior of Boron-Containing Amino Acids for Neutron CaptureTherapy in Aqueous Solutions 127

M. Kobayashi and Y. Kitaoka

Contents xvii

Carborane Related

17. Asymmetric Synthesis of o- and /?-Carboranyl Amino Acids 131J. Malmquist, J. Carlsson, K. E. Markides, P. Pettersson, P. Olsson,

K. Sunnerheim-Sjoberg, and S. Sjoberg

18. Synthesis, Tissue Uptake, and Toxicity of a NickelTetracarboranylphenylporphyrin 137

M. Miura, P. L. Micca, J. A. Donaldson, J. C. Heinrichs, J. A. Shelnutt,G. C. Finkel, and D. N. Slatkin

19. Optimization of Drug Anchor for Or/io-Carborane in Reconstitution of LowDensity Lipoproteins for Neutron Capture Therapy 143

M. D. Smith, Y. Setiawan, and D. E. Moore

20. Synthesis of 5-S-Alkylcarboranyl-2'-Deoxyuridines 151A. J. Lunato, A. K. M. Anisuzzaman, F.-G. Rong, D. H. Ives, S. Ikeda, and

A. H. Soloway

21. Synthesis of Boronated Uridine Derivatives for Boron Neutron CaptureTherapy 157

G. W. Kabalka, N. Kesavulu Reddy, and C. Narayana

DNA Related

22. New Small Molecular Weight Agents for Boron Neutron Capture Therapy 163A. H. Soloway, I. M. Wyzlic, W. Tjarks, J. A. Hariharan, M. Burgos-Fuster,

and R. F. Barth

23. Synthesis and Biochemical Evaluation of 5-Tethered Boron-ContainingPyrimidine Nucleosides for BNCT 167

F.-G. Rong, A. H. Soloway, S. Ikeda, and D. H. Ives

24. Synthesis of a Water-Soluble o-Carborane Bearing Uracil Moiety viaPalladium Catalyzed Reaction under Essentially Neutral Conditions 173

H. Nemoto, J. Cai, and Y. Yamamoto

25. Netropsin and Distamycin Analogues Bearing Ortho-Carborane 177Y. Yamamoto, J. Cai, H. Nakamura, N. Sadayori, and H. Nemoto

Neuclides Measurements

26. Spatial and Temporal Distribution of Boron Uptake in Excised Samples ofHuman Rheumatoid Synovium 183

L. S. Johnson, J. C. Yanch, S. Shortkroff, and C. B. Sledge

27. Analysis of Boron in LDL-Matrix ' 189S. Savolainen, J. Raisanen, J. Laakso, I. Ruokonen, R. Zilliacus,

J. Likonen, U. A. Ramadan, V. Etelaniemi, J. Callaway, and M. Kallio

xviii Contents

28. Non-Linear Regression between Track Density and IOB Concentration inPhoto-Electronic Neutron Capture Radiography 197

J. P. Pignol, N. Brassart, P. Chauvel, and J. C. Abbe

29. New Developments in the Use of Solid State Nuclear Track Detectors . 203S. Teichmann, J. F. Crawford, B. Larsson, and T. Suda

30. Subcellular Localization of a Boronated Nucleoside Using Ion Microscopy . . . . 209I. Gay, R. F. Schinazi, D. C. Liotta, and G. H. Morrison

31. Ion Microscopy Imaging of Boron from BNCT Drugs in CryogenicallyPrepared Tissues 215

D. R. Smith, S. Chandra, J. A. Coderre, J. L. Wilson, P. L. Micca,M. M. Nawrocky, and G. H. Morrison

32. Application of Neutron-Induced Prompt Gamma-Ray Analysis forDetermination of B-10 in BNCT 221

C. Yonezawa, H. Matsue, H. Sawahata, T. Kurosawa, M. Hoshi, and Y. Ito

33. Foundations for Boron Neutron Capture Therapy of High-Grade Astrocytomas 227L. G. Salford, C. P. Ceberg, A. Bruri, A. Persson, and R. B. R. Persson

MRS and MRI

34. Noninvasive in Vivo Detection of Boron-10 by Magnetic Resonance 233P. Bendel, J. Zilberstein, Y. Salomon, and G. W. Kabalka

35. Determination of Mn-BOPP Concentrations Using Neutron ActivationAnalysis and MRI 239

M. J. Combs, R. U. Mulder, S. S. Berr, C. Oveissi, and S. B. Kahl

36. Boron-, Gadolinium-Porphyrin Derivatives for Neutron Capture Therapy 245A. Matsumura, Y. Shibata, K. Nakagawa, T. Yamamoto, T. Yoshizawa,

Y. Yoshii, T. Nose, I. Sakata, S. Nakajima, and Naoto Miwa

37. The Measurement of Gadolinium Concentration in Rat Brain Tumor withNMR Analyzer for Neutron Capture Therapy 251

Y. Shibata, A. Matsumura, K. Nakagawa, T. Yamamoto, Y. Yoshii, T. Nose,S. Sakata, and S. Nakajima

Physics

General and Treatment Planning

38. Procedures for the Medical Application of Research Reactors 257H. Nishihara and K. Kanda

39. On-Line Beam Monitoring for Boron Neutron Capture Therapy at the MITResearch Reactor 261

O. K. Harling, D. J. Moulin, J. -M. Chabeuf, and G. R. Solares

Contents xix

40. Status of the BNCT Project at the HFR Petten 271R. L. Moss

41. Physics of Boron Neutron Capture Therapy in Japan 281K. Kanda

42. Improvements in Patient Treatment Planning Systems 289F. J. Wheeler, D. E. Wessol, R. Babcock, D. W. Nigg, C. A. Atkinson, and

J. Evans

43. Monte Carlo Neutron Photon Treatment Planning Calculations 295S. A. Wallace, B. J. Allen, and J. N. Mathur

44. Validation of Monte Carlo Dose Planning Calculations by Epithermal BeamDose Distribution Measurements in Phantoms 303

M. G. Carolan, S. A. Wallace, B. J. Allen, A. B. Rosenfeld, J. N. Mathur,H. A. Meriaty, F. Stecher-Rasmussen, R. L. Moss, C. P. J. Raaijmakers,and M. W. Konijnenberg

Neutron Source: Reactor

45. Design Study on Triangular-Hexagonal TRIGA Core for Epithermal NeutronIrradiation 311

O. Aizawa

46. Development of the ECN Argonaut Reactor for BNCT Studies 319F. Stecher-Rasmussen, C. Vroegindeweij, W. E. Freudenreich,

J. B. M. de Haas, and W. F. A. R. Verbakel

47. The Boron Neutron Capture Therapy Research Facility at the Tehran ResearchReactor (TRR) 327

M. K. Marashi and A. Pazirandeh

48. Epithermal Neutron Beam Design for Neutron Capture Therapy at Tsing HuaOpen-Pool Reactor 337

L. Su, Y-W. H. Liu, J. J. Peir, and T. F. Liaw

49. Upgrades of the Epithermal Neutron Beam at the Brookhaven MedicalResearch Reactor 343

H. B. Liu, R. M. Brugger, and D. C. Rorer

50. A Direct Comparison of Neutron Energy Spectra at High and Low Powers inthe HB11 Beam at H.F.R Petten 349

J. F. Crawford, S. Teichmann, and F. Stecher-Rasmussen

51. Conceptual Design for an Epithermal-Neutron Beam for Boron NeutronCapture Therapy at the Georgia Institute of Technology Research Reactor 357

K. A. Klee and R. A. Karam

52. Remodeling of the Heavy-Water Facility of the Kyoto University Reactor forEpithermal and Thermal Neutrons 365

T. Kobayashi, Y. Sakurai, K. Kanda, and Y. Fujita

xx Contents

53. The Utilization of Hyper-Thermal Neutrons for Neutron Capture Therapy 375Y. Sakurai, T. Kobayashi, and K. Kanda

54. Epithermal-Neutron Beam Design for Neutron Capture Therapy at theTsing-Hua Open Pool Reactor (THOR) 385

H.-M. Liu

55. The IEC Neutron Generator and Filter Concept for Neutron Capture Therapy . . 393J. H. Nadler, W. Y. Yoon, and G. H. Miley

56. Capillary Neutron Optics for Boron Neutron Capture Therapy 399Q. F. Xiao, V. A. Sharov, D. M. Gibson, H. Chen, D. F. R. Mildner, and

R. G. Downing

Neutron Source: Fission Product

57. High-Intensity Fission-Converter-Based Epithermal Neutron Beam forNeutron Capture Therapy 407

O. K. Hading and W. S. Kiger III

58. A Study of the Concept of a Fission-Plate Converter as a Source for anEpithermal Neutron Beam 413

H. B. Liu and R. M. Brugger

59. Design of Epithermal Neutron Beams Using Spent Fuel Elements at theMusashi Reactor 419

T. Matsumoto, H. B. Liu, and R. M. Brugger

Neutron Source: Accelerator and Generator

60. An Accelerator-Based Epithermal Photoneutron Source for BNCT 425D. W. Nigg, H. E. Mitchell, Y. D. Harker, W. Y. Yoon, J. L. Jones, and

J. F. Harmon

61. Conceptual Design of a Deuteron Linac Facility for Boron Neutron CaptureTherapy 431

J. Hirota, K. Ikeda, M. Sasaki, and H. Yokobori

62. Shielding Design and Dose Assessment for an Accelerator-Based BNCTFacility 439

WB. Howard and J.C. Yanch

63. Neutron Generator as a Neutron Source for BNCT 445G. Shani, L. Tsvang, S. Rozin, and M. Quastel

Contents xxi

Dosimetry

64. Beam Profiles of an Epithermal Neutron Beam 451C. P. J. Raaijmakers, M. W. Konijnenberg, and B. J. Mijnheer

65. Mixed Field Dosimetry of Neutron Beams for Boron Neutron Capture Therapyat the Massachusetts Institute of Technology 457

R. D. Rogus, O. K. Harling, and J. C. Yanch

66. Determination of Boron Dose for BNCT Using Fricke and EPR Dosimetry . . . . 467L. Wielopolski and B. Ciesielski

67. Simultaneous Monitoring System of Neutron Fluence Rate Distribution byDetectors with Multiple Sensitive Heads 473

Y. Hayakawa, Y. Nakagawa, and H. Hatanaka

Micro and Macro Dosimetry

68. Dose Sparing of Capillary Endothelial Cells for BSH and BPA 479D. E. Charlton and B. J. Allen

69. A Microdosimetry Model for BNCT Analysis 485C. Vroegindeweij, F. J. Wheeler, F. Stecher-Rasmussen, R. Huiskamp, and

D. Gabel

70. A Microdosimetry Model for in Vitro Boron Neutron Capture IrradiationExperiments Using d(14)+Be-Neutrons 495

F. Poller and W. Sauerwein

71. Computational Dosimetry of BNCT for Breast Cancer Treatment 501J. B. Weldy and J. S. Brenizer, Jr.

72. Phantoms for Neutron Capture Therapy Dosimetry 511O. K. Harling, R. D. Rogus, E. L. Redmond II, K. A. Roberts, D. J. Moulin,

and C. S. Yam

Gadolinium NCT

73. Measurements of Depth-Dose Distributions in a Phantom for GadoliniumNeutron Capture Therapy 517

T. Matsumoto and A. Tsuruno

74. Theoretical Evaluation of the Dose Distribution for Gadolinium NeutronCapture Therapy 523

J. G. Wierzbicki, D. Archambeault, and Y. Maruyama

75. Calculated Electron Spectra for Gadolinium Neutron Capture Therapy 527T. Maeda, K. Kagehira, Y. Sakurai, T. Kobayashi, K. Kanda, and Y. Akine

xxii Contents

Radiobiology

Blood-Brain Barrier

76. Biologic Considerations in Targeting Brain Tumors for Boron Neutron CaptureTherapy 533

R. F. Barth

77. Tl Measurement to Study the Penetration of BNCT Agents into CanineTumors Caused by Blood Brain Barrier Damage 541

P.-P. P. Zhu Tang, M. P. Schweizer, J. R. Hadley, S. P. Hendee,R. H. Tippets, and K. M. Bradshaw

78. Enhanced Tumor Uptake of Boronophenylalanine by Means of OsmoticBlood-Brain Barrier Disruption in Glioma-Bearing Rats 547

W. Yang, R. F. Barth, D. E. Carpenter, and J. H. Goodman

Treatment Planning

79. Boron Neutron Capture Therapy of Glioblastoma Multiforme Using the/j-Boronophenylalanine-Fructose Complex and Epithermal Neutrons 553

J. A. Coderre, R. Bergland, M. Chadha, A. D. Chanana, E. Elowitz,D. D. Joel, H. B. Liu, D. N. Slatkin, and L. Wielopolski

80. The Dose Planning of BNCT for Brain Tumors 563K. Ono, S. Masunaga, Y. Kinashi, M. Takagaki, T. Kobayashi, Y. Imahori,

S. Ueda, and Y. Oda

81. Effectiveness of Borocaptate Sodium for Boron Neutron Capture Therapy inMalignant Brain Tumors 571

M. Takagaki, Y. Oda, Y. Koda, H. Kikuchi, and K. Ono

82. Evaluation of Response to Thermal Neutron Irradiation in Quiescent CellPopulations within Murine Solid Tumors Using Micronucleus Assay 579

S. Masunaga, K. Ono, T. Kobayashi, K. Akuta, M. Akaboshi, M. Takagaki,M. Abe, and P. C. Keng

83. Assessment of Radiation Induced Damage of Mouse Brain Usingl8F-2-Deoxy-D-Glucose and 99mTc-Hexamethylpropylene Amine Oxine . . 585

Y. Abe, S. Ono, J. Takahashi, T. Sato, and H. Fukuda

84. Brain Tolerance in Dogs to Boron Neutron Capture Therapy with BorocaptateSodium (BSH) or Boronophenylalanine (BPA) 591

R. Huiskamp, P. R. Gavin, J. A. Coderre, K. H. I. Philipp, and F. J. Wheeler

Pharmacokinetics

85. Pharmacokinetics and Effects of Neutron Capture on Melanoma Xenograftsafter Administration of Boronated Low Density Lipoprotein 599

Y. Setiawan, M. D. Smith, D. E. Moore, and B. J. Allen

Contents xxiii

86. Toxicology and Pharmacokinetics of BOPP in a Canine Model 605S. B. Kahl, J. Tibbitts, and J. Fike

87. Acute Toxicity of Elaidyl-1,2,-Carborane Carboxylate (ECC) in Rats 611M. Kallio, J. Callaway, E. Saario, and S. Kahl

88. ESR Study of Hydroxyl Radicals, Superoxide Anion Radicals and MolecularSinglet Oxygen Generated by Mercaptoundecahydro-c/oso-Dodecaborate(2-) Solution Irradiated by Neutrons under Conditions ofBoron Neutron Capture Reaction 615

P. Stopka, J. Burian, and O. Strouf

89. Boron Neutron Capture Therapy of Uveal Melanoma 621J. P. Pignol, P. Chauvel, and J. C. Abbe

90. Binding and Immunohistochemical Localization of Na2B|2HnSH to TumorTissue of Glioma Patients in Boron Neutron Capture Therapy 627

B. Otersen, D. Haritz, F. Grochulla, M. Bergmann, W. Sierralta, andD. Gabel

91. Pharmacokinetics and Biodistribution in Patients with Malignant Glioma afterAdministration of N-Acetylcysteine (N-AC) prior to Borocaptate Sodium(BSH) 635

D. Haritz, B. Otersen, F. Grochulla, M. Bergmann, R. Huiskamp,D. Preusse, and D. Gabel

Newer Compounds

92. Additional Impurities Identified in Borocaptate Sodium 643W. F. Bauer, G. L. Gresham, and A. K. Gianotto

93. Uptake and Distribution of the Boron Containing Ether Lipid B-Et-11-OMe inTumor Bearing Mice 649

P. Lemmen, L. WeiBfloch, T. Auberger, and T. Probst

94. Uptake and Biological Effects of the Carborane-Based Boron CompoundsDAC-1 and DAAC-1 655

P. Olsson, P. Lindstrom, N. Tilly, M. Black, J. Malmqvist, J. Pettersson,S. Sjoberg, and J. Carlsson

Medicine

Melanoma

95. BNCT of Malignant Melanoma-Radiobiological Analysis and DataComparison with Conventional Radiotherapy 663

H. Fukuda, Y. Mishima, J. Hiratsuka,C. Honda, N. Wadabayashi,T. Kobayashi, K. Yoshino, H. K. Takahashi, Y. Abe, K. Kanda, andM. Ichihashi

xxiv Contents

96. Re-Evaluation of Skin RBE for Clinical BNCT of Malignant Melanoma 673J. Hiratsuka, H. Fukuda, T. Kobayashi, H. Karashima, K. Yoshino,

C. Honda, N. Wadabayashi, and Y. Mishima

97. Boron Analytical Studies on '"Bj-BPA Administration for Neutron CaptureTherapy of Malignant Melanoma 679

C. Honda, N. Wadabayashi, K. Yoshino, J. Hiratsuka, H. Karashima,T. Kobayashi, H. Fukuda, M. Ichihashi, and Y. Mishima

98. Pharmacokinetic Comparison between L & D, L-BPA* Fructose in a MurineMelanoma Model and in Human Patients with Metastatic Melanoma 685

D. E Moore, J. L Mallesch, W. H McCarthy, and B. J Allen

99. A Basic Concept for PET-BNCT System 691Y. Imahori, S. Ueda, Y. Ohmori, E. Yoshino, K. Ono, T. Kobayashi, T. Ido,

and Y. Mishima

100. Two Cases of Primary Malignant Melanoma Treated by Selective MelanomaThermal Neutron Capture Therapy 697

K. Watanabe, K. Ito, Y. Kaneko, S. Satake, S. Yamada, H. Yamaguchi,T. Takenouchi, M. Ito, and Yutaka Mishima

101. A Phase-I Dose-Escalation Trial of Boron Neutron Capture Therapy forSubjects with Metastatic Subcutaneous Melanoma of the Extremities . . . . 707

H. Madoc-Jones, R. Zamenhof, G. Solares, O. Harling, C-S. Yam, K. Riley,S. Kiger, D. Wazer, G. Rogers, and M. Atkins

Brain Tumors

102. Recent Study of Boron Neutron Capture Therapy for Malignant Brain Tumorin Japan 717

Y. Nakagawa and H. Hatanaka

103. Boron Neutron Capture Therapy for Malignant Brain Tumors in Children 725Y. Nakagawa, K. Pooh, T. Kageji, K. Kitamura, H. Komatsu, F. Tsuji,

H. Hatanaka, and T. Minobe

104. Blood-Brain Barrier Disruption (BBB-D) in Rats 733D. E. Carpenter, W. Yang, R. F. Barth, B. Ling, M. Castor, and

J. H. Goodman

105. A Phase 1 Trial of Intravenous Boronophenylalanine-Fructose Complex inPatients with Glioblastoma Multiforme 739

R. Bergland, E. Elowitz, J. A. Coderre, D. Joel, and M. Chadha

106. BNCT Microdosimetry and Brain-Tumor Patient Response 747M. L. Griebenow, F. J. Wheeler, C. A. Atkinson, Y. Nakagawa, G. J. Storr,

J. J. Olson, S. J. Westgate, and O. G. Orth

Contents xxv

NCT Animal Studies

107. The Therapeutic Ratio in BNCT 757J. A. Coderre, G. M. Morris, P. L. Micca, M. M. Nawrocky, C. D. Fisher,

A. Bywaters, and J. W. Hopewell

108. Boron Neutron Capture Therapy of Spontaneous Intracranial Tumors in Dogs . . 763P. R. Gavin, S. L. Kraft, C. D. Swartz, F. J. Wheeler, and W. M. Bauer

109. Sodium Borocaptate and Boronophenylalanine Alone or in Combination asCapture Agents for BNCT of the F98 Rat Glioma 769

R. F. Barth, J. H. Rotaru, A. E. Staubus, A. H. Soloway, andM. L. Moeschberger

110. BNCT as an Adjuvant to Fast Neutron Radiotherapy for Selected TumorSystems 777

G. E. Laramore, P. Wootton, D. S. Wilbur, R. Risler, M. Phillips,T. A. Buchholz, J. C. Livesey, and T. W. Griffin

111. Development of a Method to Use Boron Neutron Capture Therapy forDiffused Tumours of Liver (Taormina Project) 783

T. Pinelli, S. Altieri, F. Fossati, A. Zonta, D. Cossard, U. Prati, L. Roveda,G. Ricevuti, and R. Nano

Hazards to Organs in BNCT

112. Evidence for a Null Effect of L-'°BPA Neutron Capture Therapy on MouseBrain Dopamine Tracts 795

B. J. Allen, Y. Setiawan, D. E. Moore, G. Halliday, and T. Harding

113. Microvasculature Casting Technique for Capillary Endothelial Damage afterBNCT 803

J. Mallesch, D. E Moore, K. Narayan, and B. J Allen

114. Normal Tissue Tolerance and Fractionation Effects in Dogs of Boron NeutronCapture Irradiation with Borocaptate Sodium (BSH) 809

K. H. I. Philipp, R. Huiskamp, J. Casado, and R. L. Moss

115. The Compound Factor of Na2B|2HnSH and the Relative BiologicalEffectiveness of Recoil Protons for Neurological Damage in BoronNeutron Capture Therapy 815

D. Gabel, K. H. I. Philipp, and R. Huiskamp

MRI, PET

116. Positron Emission Tomography and Boron Neutron Capture Therapy Systemto the Patient with Malignant Brain Tumor 823

S. Ueda, Y. Imahori, Y. Ohmori, E. Yoshino, K. Ono, T. Kobayashi,M. Takagaki, Y. Oda, T. Ido, and Y. Mishima

xxvi Contents

117. Selective Detection of Brain Metastasis of Malignant Melanoma UsingI8F-'°B-L-Borono-Phenylalanine with Positron EmissionTomography 829

K. Ehara, N. Tamaki, Y. Hara,Y. Imahori, H. Horii, S. Ueda,J. Hiratsuka,and Y. Mishima

118. In Vivo NMR Evaluation of the Pharmacokinetics of Boronated Compounds inthe Rat Model 835

S. P. Hendee, K. M. Bradshaw, J. R. Hadley, P.-P. Z. Tang, andM. P. Schweizer

119. Boron MRI in a Tumor-Bearing Canine Model 843M. P. Schweizer, K. M. Bradshaw, J. R. Hadley, R. Tippets, P.-P. Z. Tang,

G. H. Glover, M. P. Heilbrun, S. Johnson, and S. P. Hendee

120. First Boron MRI of a Human Patient with a Brain Tumor 849K. M. Bradshaw, J. R. Hadley, M. P. Schweizer, M. P. Heilbrun,

W. L. Davis, and G. H. Glover

Gadolinium NCT, Cf-252 NCT

121. Assessment of Photon Contributions in Gadolinium Neutron CaptureReactions-A Preliminary Study 855

K. Tokuuye, Y. Akine, T. Kobayashi, and K. Kanda

122. Gadolinium Neutron Capture Therapy (GdNCT) with MRI Contrast Media. InVitro Studies 859

R. Lawaczeck, C. -O. Fischer, U. Kriiger, W. Leuther, andJ. Menrad

123. Neutron Capture Therapy with Gd-DTPA in Tumor-Bearing Rats 865V. F. Khokhlov, P. N. Yashkin, D. I. Silin, E. S. Djorova, and

R. Lawaczeck

124. Clinical Californium-252 Boron Neutron Capture Enhancement 871Y. Maruyama, C. Mesina, J. Wierzbicki, and A. T. Porter

Obituaries

125. Dedication to the Memory of Professor Hiroshi Hatanaka 877

126. Noted Authority on Neutron Therapy Dies in January 1995 881

Participants 883