Frontiers in Neutron Capture Therapy - Springer978-1-4615-1285-1/1.pdf · Frontiers in neutron capture therapy/edited by M. Frederick Hawthorne, Kenneth Shelly, and Richard J. Wiersema

Frontiers in Neutron Capture Therapy Volume 1

Frontiers in Neutron Capture Therapy Volume 1

Edited by

M. Frederick Hawthome Kenneth Shelly University of California, Las Angeles Las Angeles, California

and

Richard J. Wiersema Neutron Therapies LLC San Diego, California

Springer Science+Business Media, LLC

Library of Congress Cataloging-in-Publication Data

Frontiers in neutron capture therapy/edited by M. Frederick Hawthorne, Kenneth Shelly, and Richard J. Wiersema.

p. ; cm. "Proceedings of the Eighth International Symposium on Neutron Capture Therapy for

Cancer, held September 13-18,1998, in Los Angeles, California"-T.p. verso. Includes bibliographical references and index. ISBN 978-1-4613-5478-9 ISBN 978-1-4615-1285-1 (eBook) DOI 10.1007/978-1-4615-1285-1

1. Boron-neutron capture therapy-Congresses. 1. Hawthorne, M. Frederick. II. Shelly, Kenneth. III. Wiersema, Richard J. IV. International Symposium on Neutron Capture Therapy (8th: 1998: Los Ange1es, Calif.)

[DNLM: 1. Neutron Capture Therapy-Congresses. 2. Neoplasms-radiotherapy-Congresses. WN 250.5.R3 F935 2001] RC271.N48 .F76 2001 616.99' 40642-dc21

2001020257

Proceedings of the Eighth International Symposium on Neutron Capture Therapy for Cancer, held September 13-18, 1998, in Los Angeles, California

ISBN 978-1-4613-5478-9

© 2001 Springer Science+Business Media New York Originally published by Kluwer Academic/Plenum Publishers, New York in 2001 Softcover reprint ofthe hardcover Ist edition 2001

http://www.wkap.n1/

10987654321

A C.I.P. record for this book is available from the Library of Congress

Ali rights reserved

No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher

In Memoriam

Professor Borje Larsson, 1931-1998 (Photo courtesy of Jorgen Carlsson)

Borje Larsson was selected to be the Hatanaka Lecturer at the Eighth International Symposium on Neutron Capture Therapy for Cancer in recognition of his contributions to the field of NCT and radiotherapy in general. Unfortunately, he was unable to attend due to illness, and shortly after the Symposium he passed away at age 67.

Larsson was born on June 3rd 1931 in Stockholm, Sweden. His education included a BSc in biology at Stockholm University in 1955 and a MSc in electrical engineering at the Royal Institute of Technology in Stockholm, 1958. He received his docotrate from the University of Uppsala in 1962. Larsson was assistant professor (1966-1979) and professor of physical biology (1979-1991) in Uppsala. From then until 1998 he was professor of medical radiation biology at Zurich University, Switzerland. Larsson's interdisciplinary approach to science became apparent early in his career. While still a student, he was invited to work on biomedical applications for the synchocyclotron in Uppsala at the internationally known Gustaf Werner Institute (now a part of the

v

vi In Memoriam

Department of Radiation Sciences and the The Svedberg Laboratory). Larsson's careful experimental preparation paved the way for the world's first proton irradiation of a cancer patient in 1957. He continued to be a driving force in the work on irradiation of tumor patients, developing new dosimetric methods and analyzing the biological effects of protons, and he participated in new and planned accelerator centers for cancer treatment in USA, Europe and Japan.

Larsson became one of the most prominent pioneers in the development of radiation surgery. His contributions included studies on both the physical and biological aspects of radiation surgery, with clinical work on the treatments of various brain diseases including Parkinson's disease and arteriovenous blood vessel malformations. Larsson's technical leadership led to the development of radiation surgical equipment (the "gamma knife").

Larsson took an early interest in boron neutron capture therapy. He actively pursued the development of BNCT in Switzerland and Sweden, and particularly in recent years contributed to the prospect that the research reactor in Studsvik, Sweden, may be reconstructed to enable clinical treatments. Special landmarks of international recognition are his developmental work on neutron radiography and for being the initiator of the European concerted action for BNCT which in later years, through the action of Prof Detlef Gabel and others, led to the clinical BNCT research at the Petten research reactor in the Netherlands.

Besides being interdesciplinary, Larsson's approach to science was international in scope. He had numerous international collaborators, and was an adviser to many large international accelerator and reactor centers which were developed or reconstructed for biomedical purposes. He also served as guest researcher at many universities. His contributions were awarded with several national and international prizes over the years, most notably The Guldkuggen for technical development of the gamma knife, as well as the prestigious Fairchild prize, presented in Boston for developmental work in radiation surgery. Larsson also organized many international scientific meetings. He served as the President of the International Society of Neutron Capture Therapy just prior to M. F. Hawthorne, and hosted the Seventh International Symposium on Neutron Capture Therapy for Cancer in Zurich.

Borje Larsson is survived by his wife and two children, and will be missed by his relatives, friends, and colleagues. With his death, the research community has lost a valuable collaborator and a unique inspiration whose scientific contributions will leave their mark on many disciplines for years to come. Larsson was a creative researcher who through his generosity and friendliness enabled many to share his ideas and gain advantages from his achievements. For all this, we wish to express our appreciation and sincere gratitude.

Prof M. Frederick Hawthorne Department of Chemistry and Biochemistry University of California Los Angeles, USA

Prof. Jorgen Carlsson Department of Oncology, Radiobiology,

and Clinical Immunology Uppsala University, Sweden

PREFACE

The Eighth International Symposium on Neutron Capture Therapy for Cancer convened September 13-18, 1998 at the Sheraton Grande Torrey Pines Hotel in La Jolla, California. This meeting site was selected in order to enhance nascent interactions of the NCT community with the internationally recognized biotechnology companies located in La Jolla. In addition, this venue provided warm and sunny weather beside the Pacific Ocean. The Eighth International Symposium accommodated approximately 400 delegates and accompanying persons. A total of 275 lectures and posters were presented. The Seventh (Zurich) and Eighth Symposioa were quite similar in size and general content although more clinical data were available at the time of the 1988 Symposium. Clinical trials are presently in progress, planned or in temporary suspension in the United States, Japan, The Netherlands, Finland, Sweden, Eastern Europe and South America. Neutron capture therapy is clearly advancing and the Ninth Symposium, to be held in Osaka in 2000, should provide further evidence of this progress. However, at this time ipvestigators in NCT research can be justly pleased with the quality and wide scope of the papers published in these Proceedings.

The organizers of the La Jolla symposium hope the participants were rewarded both scientifically and socially. However, the illness of the Hatanaka Lecturer, Professor Borje Larsson, cast a shadow over the event. The organizers thank Dr. Nigel Crompton for his delivery of the Hatanaka Lecture on behalf of Professor Larsson.

We conclude by thanking all authors, participants and accompanying persons for their contributions and we look forward to the Ninth Symposium.

M. Frederick Hawthorne Richard J. Wiersema

Kenneth Shelly

vii

ACKNOWLEDGMENTS

The editors wish to express their gratitude to those whose assistance was vitally important in the planning and presentation of the Symposium:

Renate Alberts Ann Bates Margaret Bird Jeanne Douglas Debra A. Feakes Patrick R. Gavin Robin Green Diana Hawthorne Colin Higgs Reiko Matsuoka David W Nigg Darren Ricciardi Sherry Vatter Chris Wiersema Jean Wiersema

Symposium Sponsors The Symposium was made possible by the generous financial support from the

following organizations:

United States Department of Energy National Cancer Institute, National Institutes of Health University of California Los Angeles

Additional support was provided by the following commercial sponsors, for which we are most grateful:

Neutron Therapies (San Diego, CA) General Atomics (San Diego, CA) Callery Chemical (Pittsburgh, PA) U.S. Borax (Valencia, CA) Strem Chemical (Newburyport, MA) Ion Beam Applications (Louvain-Ia-Nueve, Belgium)

ix

x Acknowledgments

Hiroshi Hatanaka Lecture Monochromatic x-rays, slow neutrons and radionuclides for targeted radiother

apy-present developments and prospects, Borje Larsson (presented by Nigel E.A. Crompton)

Ralph G. Fairchild Awards for Young Scientists Judit Benczik, University of Helsinki Cynthia Chuang, Massachusetts Institute of Technology Andrea Wittig, University of Essen

CONTENTS

Volume 1: Medicine and Physics

INTRODUCTORY OVERVIEWS

1. Monochromatic X-rays, Slow Neutrons and Radionuclides for Targeted Radiotherapy-Present Developments and Prospects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Boerje Larsson and Nigel E. A. Crompton

2. Current Trends and Progress in the Physics of BNCT . . . . . . . . . . . . 13 David W Nigg

3. Chemistry and Pharmacology of Agents for BNCT . . . . . . . . . . . . . . 23 Debra A. Feakes

CLINICAL EXPERIENCES

4. The Harvard-MIT BNCT Program: Overview of the Clinical Trials and Translational Research . . . . . . . . . . . . . . . . . . . . . .. 37

Paul M. Busse, Robert G. Zamenhof, Otto K. Harling, Irving Kaplan, Jody Kaplan, Cynthia F. Chuang, John T. Goorley, W S. Kiger III, Kent 1. Riley, Lujia Tang, Guido R. Solares, and Matthew R. Palmer

5. Boron Neutron Capture Therapy for Glioblastoma Multiforme: Results from the Initial Phase IIII Dose Escalation Studies . . . . 61

Aidnag Z. Diaz, Arjun D. Chanana, Jacek Capala, Manjeet Chadha, Jeffrey A. Coderre, Eric H. Elowitz, Junichi Iwai, Darrel D. Joel, Hungyan B. Liu, Ruimei Ma, Noreen Pendzick, Nancy S. Peress, Magdy S. Shady, Daniel N. Slatkin, George W Tyson, and Lucian Wielopolski

xi

xii Contents

6. Boron Neutron Capture Therapy: Recent Aspects and New Protocol in Japan ................................... 73

Yoshinobu Nakagawa

7. Status Report on the European Clinical Trial of BNCT at Petten (EORTC Protocol 11961) ............................. 81

W Sauerwein, R. Moss, K. Hideghety, F. Stecher-Rasmussen, M. De Vries, H.-J. Reulen, C. Gotz, P. Paquis, F. Grochulla, K. Haselsberge, J. Wolbers, J. Rassow, J. P. Pignol, P. Watkins, C. Vroegindeweij, K. Ravensberg, S. Garbe, o. D. Wiestler, B. Turowski, F. Zanella, D. Touw, A. Siefert, R. Huiskamp, H. Fankhauser, and D. Gabel

8. Case Studies of Patients with Glioblastoma Multiforme Treated with Boron Neutron Capture Therapy at the Brookhaven Medical Research Reactor ............................ 87

E. H. Elowitz, J. Capala, J. A. Coderre, D. S. Cohen, A. Z. Diaz, D. D. Joel, and A. D. Chanana

9. Patterns of Tumor Progression Following BNCT of Glioblastoma Multiforme ....................................... 93

Aidnag Z. Diaz, Arjun D. Chanana, Jacek Capala, and Ruimei Ma

10. Intercomparison of Three Epithermal Neutron-Based Clinical Trials of BNCT .................................... 99

K. Hideghety, W Sauerwein, P. Busse, O. Harling, R. Zamenhof, A. Chanana, and J. Coderre

11. Report on the First Patient Group of the European Phase I Trial (EORTC Protocol 11961) at the High Flux Reactor Petten ........................................... 105

K. Hideghety, W Sauerwein, M. de Vries, F. Grochulla, C. Gretz, K. Haselsberger, P. Paquis, J. Heimans, J. Wolbers, R. Moss, R. Huiskamp, F. Stecher-Rasmussen, J. Rassow, S. Garbe, H. Fankhauser, and D. Gabel

12. Quality Management at the European BNCT Center in Petten 113 W Sauerwein, R. L. Moss, J. Rassow, F. Stecher-Rasmussen,

K. Hideghety, S. Garbe, J. G. Wolbers, D. Gabel, P. Watkins, C. Vroegindeweij, and H. Sack

13. Psychological Aspects of the Patient Treatment by BNCT at Petten ........................................... 123

K. Hideghety, W Sauerwein, R. Moss, M. A. Spath-Borst, J. Cassado, K.-H. Cloes, S. Blume, J. Heimans, and J. Wolbers

Contents

14. At the Threshold of Clinical Trials: The Status of the Finnish BNCT Project . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129

Markus Farkkila, Carita Aschan, liro Auterinen, Judit Benczik, Pekka Hiismaki, Juha Jaaskelainen, Eija Jarviluoma, Heikki Joensuu, Merja Kallio, Leena Kankaanranta, Mika Kortesniemi, Antti Kosunen, Petri Kotiluoto, Martti Kulvik, Juha Laakso, Seppo Pakkala, Merja Rasilainen, Seppo Salmenhaara, Sauli Savolainen, Tiina Seppala, Tom Seren, Marjatta Snellman, Marika Suominen, Mikko Tenhunen, Matti Toivonen, Leena Tahtinen, and Jyrki Vahatalo

15. An Autopsy Report of a Glioblastoma Case after Boron Neutron Capture Therapy: Comparison of MRI and Autopsy Findings. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 133

Kei Nakai, Akira Matsumura, Yasushi Shibata, Tetsuya Yamamoto, Shingo Takano, Tadao Nose, Yukinori Inadome, and Masayuki Noguchi

16. Long Term Follow Up in Patients Who Underwent Boron Neutron Capture Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 141

Yoshinobu Nakagawa, Pooh Kyonghon, Katsuji Kitamura, Teruyoshi Kageji, and Takashi Minobe

17. A Case of Astrocytoma: Twelve Year History after BNCT . . . . . . .. 145 Shuji Kamano

TREATMENT PLANNING AND CLINICAL CONSIDERATIONS

18. Treatment Planning for the First Group of Patients in the European Glioma Trial at the HFR Petten . . . . . . . . . . . . . . . . . . . . . . .. 153

C. Vroegindeweij , P. Watkins, K. Hideghety, W Sauerwein, and R. L. Moss

19. Quality Assurance for Clinical Dosimetry of the European Trial on BNCT in Petten . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 161

1. Rassow, F. Stecher-Rasmussen, K. Appelman, S. Garbe, 1. Morrissey, R. Moss, K. Ravensberg, F. Roserot de Melin, W Sauerwein, C. Vroegindeweij, and P. Watkins

20. Medical Image Transfer and Conversion for BNCT Treatment Planning at Petten . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 173

p. Watkins and C. Vroegindeweij

21. Patient Positioning at the HFR Petten. . . . . . . . . . . . . . . . . . . . . . . . 179 P. Watkins, C. Vroegindeweij, S. Garbe, and K. Hidegh6ty

xiii

xiv Contents

22. Treatment Planning Based on Dynamic Positron Emission Tomography for Boron Neutron Capture Therapy for Glioblastoma Multiforme. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 185

T. L. Nichols, G. W. Kabalka, G. T. Smith, J. P. Dyke, D. Longford, and K. F. Hubner

23. Acceleration of MCNP-Based Treatment Planning and the Application for In Vivo Boron Determination by the Gamma-Ray Telescope. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 189

W. F. A. R. Verbakel, J. A. A. Verwey, F. Stecher-Rasmussen, and A. Hogenbirk

24. Integrated Medical Image Registration, Patient Positioning, and Patient Monitoring for Cranial BNCT . . . . . . . . . . . . . . . . . .. 195

M. R. Palmer, W. S. Kiger, C. Zuo, L. P. Panych, C. R. G. Guttmann, R. G. Zamenhof, and P. M. Busse

25. Treatment Plan Evaluation in Boron Neutron Capture Therapy. . . .. 201 N. Gupta, R. A. Gahbauer, and T. E. Blue

26. A Comparison of Two BNCT Treatment Planning Programs: MacNCTPlan and BNCT _RTPE . . . . . . . . . . . . . . . . . . . . . .. 207

T. Goorley,F. Wheeler, J. Capala, W. S. Kiger III, M. Palmer, and R. Zamenhof

27. Three Dose Calculation Codes Applied to Neutron Transport in BNCT .. ......................................... 213

Juha S. Lampinen, Tiina Seppala, Iiro Auterinen, and Sauli Savolainen

28. Source Characterization for the rtCMC Treatment Planning Program at FiR 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 219

Tiina SeppaUi, Tom SenSn, and Iiro Auterinen

29. "CARONTE", A Treatment Planning System Based on Real Macroscopic Boron Distribution and MCNP-4A Code: Results and Discussion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 225

N. Cerullo and G. Daquino

30. CASE-MATE: Computer-Aided Cell Seeding, Microcloning, Analysis, and Telemetric Evaluation Applied to Neutron Capture Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 231

N. E. A. Crompton, J. Gobrecht, C. Higgs, G. Kuehne, E. Lehmann, H. Reist, J. Stepanek, T. Suda, and B. Larsson

31. Standard Operating Procedures Followed by the Petten BNC-Team during Patient Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 237

R. L. Moss, F. Stecher-Rasmussen, w. Sauerwein, D. Gabel, P. Watkins, and C. Vroegindeweij

Contents xv

32. Predicting Boron-lO Concentrations in Normal Brain and GBM from Blood Measurements. . . . . . . . . . . . . . . . . . . . . . . . . . . . 243

M. R. Palmer, C. Chuang, W S. Kiger, P. M. Busse, and R . G. Zamenhof

33. A Pharmacokinetic Model for the Concentration of Boron-IO in Blood Following Boronophenylalanine-Fructose Administration in Humans . . . . . . . . . . . . . . . . . . . . . . . . . . .. 249

W S. Kiger III, M. R. Palmer, R . G. Zamenhof, and P. M. Busse

34. Quality Control for Na2B12HIlSH, a Drug for Boron Neutron Capture Therapy in EORTC Trial 11961 . . . . . . . . . . . . . . . . .. 257

Detlef Gabel, Daan Touw, Finn Stecher-Rasmussen, Rene Huiskamp, and Wolfgang Sauerwein

35. The Pharmacokinetics of BSH Following Single and Multiple Administrations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261

Detlef Gabel, Els Winter-van Kampen, Finn Stecher-Rasmussen, Wolfgang Sauerwein, Katalin Hideghety, Frank Grochulla, Claudia Goetz, Klaus Haselsberger, Philippe Paquis, John Wolbers, and Daan Touw

REACTOR NEUTRON SOURCES AND FACILITIES

36. Metamorphosis of a 35 Year-Old TRIGA Reactor into a Modern BNCT Facility. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267

Iiro Auterinen, Pekka Hiismaki, Petri Kotiluoto, Rolf 1. Rosenberg, Seppo Salmenhaara, Tiina Seppala, Tom Seren, Vesa Tanner, Carita Aschan, Mika Kortesniemi, Antti Kosunen, Juha Lampinen, Sauli Savolainen, Matti Toivonen, and Petteri Valimaki

37. Status of the Medical Irradiation Facility at JRR-4. . . . . . . . . . . . . . 277 T. Kishi, Y. Torii, H. Kumada, K. Yokoo, N. Ohhashi,

and F. Sakurai

38. Clinical Protocol Using New Neutron Irradiation Facility (JRR4) at JAERI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283

Akira Matsumura, Yasushi Shibata, Tetsuya Yamamoto, Shingo Takano, Yoshinori Hayakawa, Kei Nakai, Yoshinobu Nakagawa, Fumio Sakurai, Yoshiya Torii, Kenji Yokoo, Hiroaki Kumada, Toshiaki Kishi, Kazuyoshi Yamamoto, Yasuyuki Akine, and Tadao Nose

39. Upgrade of the Epithermal Neutron Beam Using 235U Fission Plates at Brookhaven Medical Research Reactor (BMRR). . . .. 289

D. Rorer, F. Patti, R. Ma, A. D. Chanana, and H. B. Liu

xvi Contents

40. TRIGA ® Fuel Based Converter Assembly Design for a Dual-Mode Neutron Beam System at the McClellan Nuclear Radiation Center ............ . ......... .. .. . . .. ... . .... . .... 295

H. B. Liu, J. Razvi, R. Rucker, R. Cerbone, M. Merrill, W Whittemore, D. Newell, S. Autry, W Richards, and J. Boggan

41. BNCT Filter Design Studies at the CEA-Saclay ISIS Research Reactor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 301

F. Colomb, H. Carcreff, and C. Morin

42. Preparation of a Beam Tube of the Portuguese Research Reactor to be Used in BNC and Other Activites . . . . . . . . . . . . . . . . .. 307

A. Ramalho, I. F. Gonl;alves, I. C. Gonl;alves, J. Salgado, M. Castro, and A. F. P. Fernandes

43. NCT Facility Development and Beam Characterisation at the RA-6 Reactor. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 313

H. R. Blaumann, O. Calzetta Larrieu, J. M. Longhino, and A. F. Albornoz

44. A NCT Facility Design at HANARO . . . . . . . . . . . . . . . . . . . . . . . . 319 Byung lin lun and Byung Chul Lee

45. Beam Collimator Design for the Epithermal Neutron Beam at the Tsing Hua Open-Pool Reactor (THOR) . . . . . . . . . . . . . . . . .. 325

Hong-Ming Liu

46. The Usage of the KUR Advanced Clinical Irradiation System for NCT under the KUR Continous Operation ............... 331

Tooru Kobayashi, Yoshinori Sakurai, Keiji Kanda, and Koji Ono

47. Feasibility of the Utilization of BNCT in Thermalizing Column of TRIGA Reactor. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 337

Marko Maucec

48. The Characteristics of the Updated Heavy Water Facility of the Kyoto University Reactor (II) (Neutron Energy Spectra for Several Irradiation Modes) . . . . . . . . . . . . . . . . . . . . . . . . . . .. 345

Yoshinori Sakurai, Tooru Kobayashi, and Katsuhei Kobayashi

49. The Test-Type Hyper-Thermal Neutron Generator for Neutron Capture Therapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 351

Yoshinori Sakurai and Tooru Kobayashi

50. What are the Best Energies for Neutron Production for NCT? . . . . . . 357 J. F. Crawford and D. Suwannakachorn

Contents xvii

51. The Use of Polyterafluoroethylene (Teflon®) Containing Filter/ Moderators for Epithermal Neutron Beam Production. . . . . .. 363

Otto K. Harling, Gordon Kohse, Kent 1. Riley, and Shuichi Sakamoto

52. Three-Dimensional Measurement of Thermal Neutron Absorbed Dose for BNCT Experimental Program, Performed in a Fast Research Reactor. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 369

G. Gambarini, S. Agosteo, P. Marchesi, E. N ava, A. Pecci and G. Rosi

53. Validation of the Specification of the Epithermal Neutron Beam for Boron Neutron Capture at the HFR Petten. . . . . . . . . . . .. 375

C. Vroegindeweij, P. Watkins, and R. L. Moss

54. Determination of the Geometric and Spectral Characteristics of BNCT Beam (Neutron and Gamma-Ray) ................. 381

M. Marek, L. Viererbl, 1. Burian, and B. Jansky

55. BNCT Beam Quality Maximization E. Greenspan and Y Karni

56. A Biological Comparison of Neutron Beams Used for BNCT

391

Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 407 C. Mansfield, 1. W Hopewell, T. D. Beynon, and R. Huiskamp

57. A Comparison of Neutron Fields for BNCT. . . . . . . . . . . . . . . . . .. 413 Jeffrey E. Woollard, Thomas E. Blue, and Jacek Capala

58. The BNCT Project in the Czech Republic before the Start of Clinical Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 419

1. Burian, M. Marek, 1. Rataj, K. Prokes, F. Novy, F. Tovarys, V Dbaly, 1. Honzatko, I. Tomandl, and o. Kriz

59. The Russian Project on Neutron Capture Therapy for Cancer. . . . .. 425 V F. Khokhlov, V N. Kulakov, K. N. Zaitsev,

Yu. S. Riaboukhine, S. P. Yarmonenko, O. N. Deineko, and V N. Koienko

ACCELERATORS AND OTHER NEUTRON SOURCES

60. Development of an Accelerator-Based BNCT Facility at the Berkeley Lab . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 435

B. A. Ludewigt, D. L. Bleuel, W T. Chu, R. 1. Donahue, 1. Kwan, L. L. Reginato, and R. P. Wells

61. The Relationship between BNCT Neutron Beam Parameters and Treatment Planning Figures-of-Merit . . . . . . . . . . . . . . . . . . .. 441

D. A. Allen and T. D. Beynon

xviii Contents

62. Development of a High-Power Water-Cooled Beryllium Target for use in Accelerator-Based Boron Neutron Capture Therapy. . .. 449

Brandon W Blackburn, Jacquelyn e. Yanch, and Robert E. Klinkowstein

63. A Sealed-Accelerator-Tube Neutron Generator for Boron Neutron Capture Therapy Application. . . . . . . . . . . . . . . . . . . . . . . . .. 455

K. N. Leung, Y. Lee, 1. M. Verbeke, 1. Vujic, M. D. Williams, L. K. Wu, and N. Zahir

64. Construction of an Accelerator-Based Neutron Beamline for Treatment of Arthritic Joints. . . . . . . . . . . . . . . . . . . . . . . . .. 461

David P. Gierga, Jacquelyn e. Yanch, Ruth E. Shefer, and Brandon W Blackburn

65. Use of the 9Be(d,n) Nuclear Reaction for Accelerator-Based Boron Neutron Capture Therapy. . . . . . . . . . . . . . . . . . . . . . . . . . .. 469

S. M. White, R. E. Klinkowstein, 1. e. Yanch, K. D. Held, and K. 1. Riley

66. An Experimental Program for BNCT Using a Thermal Accelerator-Based Source and the Epithermal Facility at the Tapiro Reactor. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 475

S. Agosteo, P. Colautti, K. W Burn, S. Cevolani, F. d'Errico, E. Fantuzzi, G. Fortuna, G. Gambarini, A. Pisent, G. Rosi, e. R. Rossi, R. Tinti, and G. Tornielli

67. Investigation of 2H(d,n) 3He and 3H(d,n) 4He Fusion Reactions as Alternative Neutron Sources for BNCT . . . . . . . . . . . . . . . . . . 483

1. M. Verbeke, 1. Vujic, and K. N. Leung

68. Spectral Characterization of Accelerator-Based Beams for BNCT Using Neutron Activation Foils. . . . . . . . . . . . . . . . . . . . . . .. 489

L. G. Murphy, 1. e. Yanch, and D. W Nigg

69. Preliminary Study on Accelerator-Based Neutron Fields for NCT: Au-Activity Distributions in a Water Phantom with Two Types of Accelerators. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 495

Kenichi Tanaka, Yoshinori Sakurai, Tooru Kobayashi, Yoshinobu Nakagawa, Satoru Endo, and Masaharu Hoshi

70. Experimental in-Phantom Dosimetry of the 7Li(p,n) Reaction Near Threshold .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 503

David P. Gierga, Susan M. White, Robert E. Klinkowstein, Charles L. Lee, and Jacquelyn C. Yanch

71. Feasibility of a Near-Threshold BNCT Neutron Source Based on Phantom Dosimetry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 509

e. L. Lee, R. 1. Kudchadker, F. Harmon, x.-L. Zhou, and Y. D. Harker

Contents xix

72. Analysis of Accelerator Based Neutron Spectra for BNCT Using Proton Recoil Spectroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . 515

L. Wielopolski, H. Ludewig, J. R. Powell, D. Raparia, J. G. Alessi, and D. I. Lowenstein

73. Energy Optimization of Epithermal Neutron Beams for Accelerator-Based BNCT. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 523

E. Bisceglie, P. Colangelo, N. Colonna, G. Maggipinto, V. Paticchio, G. Raso, P. Santorelli, and V. Variale

74. Applications of Californium-252 and the Californium User Facility for Neutron Capture Therapy Research. . . . . . . . . . . . . . . . . . . 529

R . C. Martin, C. W Alexander, C. M. Simmons, and D. L. Marsh

75. Neutronic Design of a mCf_235U Epithermal Irradiation Facility Applied to BNCT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 535

A. P. Andrade and T. P. R. Campos

76. Measurement of Fast Neutron, Gamma, and Thermal Neutron Dose Around a Cf-252 Source . . . . . . . . . . . . . . . . . . . . . . . .. 539

Somsak Wanwilairat, Thiraphat Vilaithong, Vicharn Lorvidhaya, Rainer Schmidt, and Wilfried Hoffmann

77. Calculated Boron Neutron Capture Dose Enhancement in ICRU 44 Brain with mCf. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 547

Mark J. Rivard, Laurie E. Gaspar, and Jacek G. Wierzbicki

DOSIMETRY

78. Semiconductor Dosimetry in BNCT: Present and Future. . . . . . . . . . 557 Anatoly B. Rosenfeld

79. Reporting a BNCT Irradiation: Application of the ICRU Recommendations to the Specific Situation in BNCT . . . . . . .. 565

R. Gahbauer, N. Gupta, T. Blue, D. Carpenter, W Sauerwein, and A. Wambersie

80. Radiation Risks fromp-Boronophenylalanine-Mediated BNCT for Glioblastoma Multiforme . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 571

R . Ma, J. Capala, J. Coderre, A. Z. Diaz, D. Greenberg, H. B. Liu, D. N. Slatkin, and A. D. Chan ana

81. Nominal Effective Radiation Doses Delivered to the Tumor and Different Parts of the Normal Brain During BNCT for Glioblastoma Multiforme. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 575

J. Capala, J. A. Coderre, A. Z. Diaz, R. Ma, and A. D. Chan ana

xx Contents

82. Microdosimetry Studies at the BMRR and the MITR-II Using Miniature Tissue-Equivalent Proportional Counters ........ . 581

I Burmeister, C. Kota, R . L. Maughan, K . Riley, O. Harling, L. Wielopolski, R. Ma, and I Coderre

83. Radiation Dosimetry for NCT Facilities at the Brookhaven Medical Research Reactor . .. . . . ................... ... ...... . 587

N. E. Holden, I-P' Hu, D. D. Greenberg, and N. Reciniello

84. In Vivo Determination of Boron in Patients During BNCT in Petten by Means of the Gamma-Ray Telescope .................. 593

w. F. A. R . Verbakel and F. Stecher-Rasmussen

85. MCNP Enhancements, Parallel Computing, and Error Analysis for BNCT ........... . ............................ 599

T. Goorley, G. McKinney, K. Adams, and G. Estes

86. Calculation of Absorbed Dose Distributions Using Removal-Diffusion Theory for BNCT Treatment Planning . ...... . .. . 605

B. Albertson, I Niemkiewicz, T. E. Blue, and N. Gupta

87. The Development of a Computational Dosimetry System for BNCT at JAERI . . .. ... . . .. ... . .. . . ..... . .. . ... . .. . 611

H. Kumada, Y Torii, K. Saito, Y Yamaguchi, A. Matsumura, Y Nakagawa, and F. Sakurai

88. Application of Silicon Diode Arrays for Microdosimetry in BNCT and FNT .... . ... ..... . ....... ... .. . ...... .. . . .... 615

Peter D. Bradley, Anatoly B. Rosenfeld, Barry I Allen, Tooru Kobayashi, Yoshinori Sakurai, Chandrasekhar Kota, Richard L. Maughan, Mark Yudelev, Jeffrey Coderre, and Jacek Capala

89. Shielding Design and Calculations for the Finnish BNCT Facility ... 623 Petri Kotiluoto, Pekka Hiismaki, liro Auterinen, Tiina Seppala,

and Carita Aschan

90. NCT Treatment Room Dose Determinations Using the Monte Carlo Adjoint Shielding (MASH) Method . . . . .. . ......... 629

R. A. Rydin, T. R. Hubbard, and R. U. Mulder

91. Radioprotection for Patients and Staff during BNCT at the HFR Petten ... . . ..... . .. ... ... ..... .... .. ... . ....... . . 635

R. L. Moss, F. Stecher-Rasmussen, K. Appelman, I Lutgerink, A. Keverling-Buisman, I Rassow, and W Sauerwein

92. Real-Time Absorbed Dose Estimation System for BNCT by PG-SPECT . . . ..... . .. . .. ..... . ....... .. .. .. .. . . .. . 641

Tooru Kobayashi, Yoshinori Sakurai, and Masayori Ishikawa

Contents xxi

93. Utility of Measured Microdosimetric Single Event Spectra in Interpreting Quality of Radiation Fields Used in BNCT ...... 647

Chandrasekhar Kota, Jay Burmeister, and Richard Maughan

94. Cell Cluster Models for Microdosimetry ....................... 653 Petteri Viilimiiki, Juha Lampinen, Antti Kuronen,

and Sauli Savolainen

95. Measurements of Phantom Dose Distributions at the Finnish BNCT Facility ..................................... 659

Mika Kortesniemi, Antti Kosunen, Carita Aschan, Tom Seren, Petri Kotiluoto, Matti Toivonen, Petteri Valimaki, Tiina Seppala, liro Auterinen, and Sauli Savolainen

96. Radioprotection Dosimetry in the European Trial on BNCT Studied by an Anthropomorphic Phantom ................ 665

S. Garbe, 1. Rassow, C. Vroegindeweij, R. Moss, K. Hideghety, W Sauerwein, C. Kessler, and F. Stecher-Rasmussen

97. Development of a Neutron Energy-Biased in-Air Figure-of-Merit for Predicting in-Phantom BNCT Neutron Beam Characteristics ..................................... 671

D. L. Bleuel, R. 1. Donahue, B. A. Ludewigt, and 1. Vujic

98. Reference Phantom Design for the Birmingham BNCT Project ..... 681 C. Wojnecki and S. Green

99. Absorbed Dose Estimates with a High Resolution Voxel-Based Head Phantom ..................................... 687

Jeffrey F. Evans, Thomas E. Blue, and Nilendu Gupta

FAST NEUTRON STUDIES

100. Neutron Capture Therapy (NCT) Enhancement of Fast Neutron Radiotherapy at the University of Washington: Past, Present, and Future Directions ............................... 695

George E. Laramore and Keith 1. Stelzer

10l. Progress towards Boron Neutron Capture Enhancement of Fast Neutron Therapy at the Harper Hospital Neutron Therapy Facility .................................... 703

Richard L. Maughan, Chandrasekhar Kota, Jay Burmeister, Kenneth 1. Levin, Paul 1. Chuba, Laurie E. Gaspar, and Jeffrey D. Forman

102. Characterization of a Modified Fast Neutron Beam for Boron Neutron Capture Enhancement of Fast Neutron Therapy ..... 709

1. Burmeister, C. Kota, M. Yudelev, and R. L. Maughan

103. Modifications to rtCMC for Fast Neutron Therapy Treatment Planning ......................................... 715

C. A. Wemple, F. 1. Wheeler, and D. W Nigg

xxii Contents

104. Treatment Planning for Boron Neutron Capture-Enhanced Fast Neutron Therapy ................................... 723

Chandrasekhar Kota, Jay Burmeister, Richard Maughan, Kenneth Levin, Paul Chuba, Laurie Gaspar, and Jeffrey Forman

105. Modification of the University of Washington Neutron Radiotherapy Facility for Optimization of NeutronCapture-Enhanced Fast Neutron Therapy. . . . . . . . . . . . . . . .. 729

D. W Nigg, C. A. Wemple, R. Risler, J. K. Hartwell, Y. D. Harker, and G. E. Laramore

106. Boron Neutron Capture-Enhanced Fast Neutron Therapy (BNC/FNT) for Non-Small Cell Lung Cancer in Canine Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 735

K. J. Stelzer, P. R. Gavin, R. Risler, H. Kippenes, M. F. Hawthorne, D. W Nigg, and G. E. Laramore

107. BNCEFN Optimisation with Lead Blocks Collimation and Graphite Embedding: The Monte Carlo Simulation of Various Fast Neutron Beams Intercomparison . . . . . . . . . . . .. 741

Jean-Philippe Pignal, Philippe Paquis, Roland Sabattier, Arlene Lennox, Thomas Kroc, Dan Jones, Jakobus Slabbert, Cheikh M. B. Diop, Gilbert Blondiau, and Noel Breteau

108. On the Study of a Laminated Beryllium/Tungsten Target for Boron Neutron Capture Enhanced Fast-Neutron Therapy ......... , 747

Richard Oberer, C.-K. Chris Wang, and Lisa Chiang

109. Progress Toward Fast Neutron Relative Biological Effectiveness Determination Via Proton Bombardment of V79 Cells. . . . . .. 755

M. A. Sitek, J. C. Yanch, R. E. Klinkowstein, H. Song, and K. D. Held

Author Index, Vol. 1 .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. XXlll

Keyword Index, Vol. 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxvii

Frontiers in Neutron Capture Therapy

Volume 2

Frontiers in Neutron Capture Therapy

Volume 2

CONTENTS

Volume 2: Chemistry and Radiobiology

CHEMISTRY AND SYNTHESIS

110. A Concise Synthesis of Enantiomerically Pure L-( 4-Boronophenyl)alanine from L-Tyrosine . . . . . . . . . . . . . .. 765

Hiroyuki Nakamura, Masaru Fujiwara, and Yoshinori Yamamoto

111. The Complexation of p-Boronophenylalanine with Alcohols or Carboxylic Acids Studied by Zone Electrophoresis. . . . . . . . .. 769

Yoshinori Kitaoka and Mitsue Kobayashi

112. Recent Developments in the Chemistry of [BI2H I2f- . . . . . . . . . . . .. 775 Toralf Peymann, Kenneth Shelly, and M. Frederick Hawthorne

113. Synthesis of Schiff Bases and Monoalkylamino Derivatives on the Base of Amino-closo-Dodecaborate(l-) Anion [B12HllNH3r . .. 779

Igor B. Sivaev, Aleksandr B. Bruskin, Vladimir V. Nesterov, Mikhail Yu Antipin, Vladimir 1. Bregadze, and Stefan Sjoberg

114. Potential BNCT Agents: Synthesis of Boron-Containing Pyrimidine Nucleoside and Approaches in the Synthesis of 4-Borauracil. .. 785

Jin-Cong Zhuo, Albert H. Soloway, Beverly A. Barnum, and Werner Tjarks

115. Borylated Ferrocenium Compounds: Potential New Drugs for BNCT? .......................................... 791

L. Weissfloch, M. Nagl, M. Wagner, T. Probst, D. Preusse, P. Nilsson, R. Senekowitsch-Schmidtke, D. Gabel, J. Carlsson, K. Tempel, and M. Molls

116. Enantioselective Syntheses of lOB-Enriched L- and D-Carboranylalanine and Their Radiobiological Evaluation in V-79 Chinese Hamster Cells . . . . . . . . . . . . . . . . . . . . . . . .. 797

Stephen B. Kahl, John J. Schaeck, Brenda Laster, and Lynn Warkentien

xxxi

CONTENTS

Volume 2: Chemistry and Radiobiology

CHEMISTRY AND SYNTHESIS

110. A Concise Synthesis of Enantiomerically Pure L-( 4-Boronophenyl)alanine from L-Tyrosine . . . . . . . . . . . . . .. 765

Hiroyuki Nakamura, Masaru Fujiwara, and Yoshinori Yamamoto

111. The Complexation of p-Boronophenylalanine with Alcohols or Carboxylic Acids Studied by Zone Electrophoresis. . . . . . . . .. 769

Yoshinori Kitaoka and Mitsue Kobayashi

112. Recent Developments in the Chemistry of [BI2H I2f- . . . . . . . . . . . .. 775 Toralf Peymann, Kenneth Shelly, and M. Frederick Hawthorne

113. Synthesis of Schiff Bases and Monoalkylamino Derivatives on the Base of Amino-closo-Dodecaborate(l-) Anion [B12HllNH3r . .. 779

Igor B. Sivaev, Aleksandr B. Bruskin, Vladimir V. Nesterov, Mikhail Yu Antipin, Vladimir 1. Bregadze, and Stefan Sjoberg

114. Potential BNCT Agents: Synthesis of Boron-Containing Pyrimidine Nucleoside and Approaches in the Synthesis of 4-Borauracil. .. 785

Jin-Cong Zhuo, Albert H. Soloway, Beverly A. Barnum, and Werner Tjarks

115. Borylated Ferrocenium Compounds: Potential New Drugs for BNCT? .......................................... 791

L. Weissfloch, M. Nagl, M. Wagner, T. Probst, D. Preusse, P. Nilsson, R. Senekowitsch-Schmidtke, D. Gabel, J. Carlsson, K. Tempel, and M. Molls

116. Enantioselective Syntheses of lOB-Enriched L- and D-Carboranylalanine and Their Radiobiological Evaluation in V-79 Chinese Hamster Cells . . . . . . . . . . . . . . . . . . . . . . . .. 797

Stephen B. Kahl, John J. Schaeck, Brenda Laster, and Lynn Warkentien

xxxi

xxxii Contents

117. A Potential New BNCT Agent: Galactose Containing l-Amino-3[2-(1,7-Dicarba-closo-Dodecaboran-l-yl)Ethyl]Cyc1obutanecarboxylic Acid. . . . . . . . . . . . . . . . . . . . . . . . . .. 803

G. W Kabalka, G. Li, and R. R. Srivastava

118. Benzoquinone Oxidation of the [ae-B2oH 17NH3]3- and [ae-B20H 170Ht- Ions .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 807

Fangbiao Li, Kenneth Shelly, Carolyn B. Knobler, and M. Frederick Hawthorne

119. BSMel: An Aromatic Amino Acid Analog of High Boron Content, Easily Prepared from B-lO Enriched and Stereochemically Pure Precursors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 813

John D. Glass, Michael S. Makar, and Jeffrey A. Coderre

120. Current Status of Selenium Coupling to Hoechst-Carborane. . . . . .. 819 Deborah de F. dos Santos, Mario Argentini, Regin Weinreich,

and Hans-Jiirgen Hansen

121. New Synthesis of Boronated Chlorins with Different Lipophilicity. .. 825 Silke Ruf, Jens Osterloh, and Detlef Gabel

122. Fluorination of p-Boronophenylalanine. . . . . . . . . . . . . . . . . . . . . .. 831 Kazuo Yoshino, Yoshiro Inamoto, Tatsuo Ido,

Hidetake Kakihana, Masamitsu Ichihashi, and Yutaka Mishima

123. Radioiodination Techniques for Aromatic Amino Acids: Possible Tracers for BPA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 835

J. Vlihiitalo, M. Kulvik, S. Savolainen, and S.-L. Karonen

124. Synthetic Approaches to a Novel Iodinated Analogue of BPA. . . . .. 839 M. Suominen, J. Vlihlitalo, J. Yli-Kauhaluoma, and T. Hase

125. Design of Boron- and Gadolinium-Containing Agents for NCT . . .. 843 V. N. Kulakov, V. I. Bregadze, I. B. Sivaev, S. M. Nikitin,

Yu. V. Gol'tyapin, and V. F. Khokhlov

IMAGING AND ANALYSIS OF NUCLIDES

126. On-Line Boron-IO Determination from Blood Samples by ICP-MS .. 849 M. Kulvik, J. Laakso, J. Vlihlitalo, and R. Zilliacus

127. The Role of Dynamic Positron Emission Tomography for Quantifying Boron-IO in Vivo Using the Fructose Complex of Fluorine-18 Labeled Boronophenylalanine . . . . . . . . . . . . .. 853

G. W Kabalka, G. T. Smith, T. L. Nichols, J. P. Dyke, D. Longford, and K. F. Hubner

xxxii Contents

117. A Potential New BNCT Agent: Galactose Containing l-Amino-3[2-(1,7-Dicarba-closo-Dodecaboran-l-yl)Ethyl]Cyc1obutanecarboxylic Acid. . . . . . . . . . . . . . . . . . . . . . . . . .. 803

G. W Kabalka, G. Li, and R. R. Srivastava

118. Benzoquinone Oxidation of the [ae-B2oH 17NH3]3- and [ae-B20H 170Ht- Ions .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 807

Fangbiao Li, Kenneth Shelly, Carolyn B. Knobler, and M. Frederick Hawthorne

119. BSMel: An Aromatic Amino Acid Analog of High Boron Content, Easily Prepared from B-lO Enriched and Stereochemically Pure Precursors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 813

John D. Glass, Michael S. Makar, and Jeffrey A. Coderre

120. Current Status of Selenium Coupling to Hoechst-Carborane. . . . . .. 819 Deborah de F. dos Santos, Mario Argentini, Regin Weinreich,

and Hans-Jiirgen Hansen

121. New Synthesis of Boronated Chlorins with Different Lipophilicity. .. 825 Silke Ruf, Jens Osterloh, and Detlef Gabel

122. Fluorination of p-Boronophenylalanine. . . . . . . . . . . . . . . . . . . . . .. 831 Kazuo Yoshino, Yoshiro Inamoto, Tatsuo Ido,

Hidetake Kakihana, Masamitsu Ichihashi, and Yutaka Mishima

123. Radioiodination Techniques for Aromatic Amino Acids: Possible Tracers for BPA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 835

J. Vlihiitalo, M. Kulvik, S. Savolainen, and S.-L. Karonen

124. Synthetic Approaches to a Novel Iodinated Analogue of BPA. . . . .. 839 M. Suominen, J. Vlihlitalo, J. Yli-Kauhaluoma, and T. Hase

125. Design of Boron- and Gadolinium-Containing Agents for NCT . . .. 843 V. N. Kulakov, V. I. Bregadze, I. B. Sivaev, S. M. Nikitin,

Yu. V. Gol'tyapin, and V. F. Khokhlov

IMAGING AND ANALYSIS OF NUCLIDES

126. On-Line Boron-IO Determination from Blood Samples by ICP-MS .. 849 M. Kulvik, J. Laakso, J. Vlihlitalo, and R. Zilliacus

127. The Role of Dynamic Positron Emission Tomography for Quantifying Boron-IO in Vivo Using the Fructose Complex of Fluorine-18 Labeled Boronophenylalanine . . . . . . . . . . . . .. 853

G. W Kabalka, G. T. Smith, T. L. Nichols, J. P. Dyke, D. Longford, and K. F. Hubner

Contents xxxiii

128. Structure Determination of p-Boronophenylalanine-Fructose Complex Using llcc Coupling Constants. . . . . . . . . . . . . . . .. 857

Miyuki Kitazawa and Kazuo Yoshino

129. Simultaneous Determination of p-Boronophenylalanine and Boric Acid Using "B-NMR ................................ 863

Kazuo Yoshino, Yasuhito Tanaka, Hidetake Kakihana, Masamitsu Ichihashi, and Yutaka Mishima

130. Structure of the BPA-Fructose Complex: A C-13 NMR Investigation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 869

P. Bendel, C. Anderson, and G. W Kabalka

131. Proton MR Spectroscopic Measurement of p-Boronophenylalanine for in Vivo Pharmacokinetic Studies: A Preliminary Study. . . .. 875

C. S. Zuo, P. V. Prasad, L. Tang, N. Adnani, and R. G. Zamenhof

132. Subcellular Localization of BSH-Containing and Non-BoronContaining Chlorin Derivatives in Living Cells Using Confocal Laser Scanning Microscopy. . . . . . . . . . . . . . . . . . .. 883

Stefanie Steen-Ecke, Franz-Peter Montforts, and Detlef Gabel

133. Quantitative Analysis of Boron in Co-Cultures of Human Glioblastoma T98G Cells and Normal Cell Lines within the Same Field of View of Ion Microscopy Imaging. . . . . . . . . . .. 887

Daniel R. Lorey II, Subhash Chandra, Duane R. Smith, and George H. Morrison

134. Ion Microscopy Imaging of Boron in Animal Tissue Sections for Neutron Capture Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . .. 893

Duane R. Smith, Darrel D. Joel, Jeffrey A. Coderre, Gerard M. Morris, Subhash Chandra, Marta M. Nawrocky, Peggy L. Micca, Hemant Patel, and George H. Morrison

135. Ion Microscopy Imaging of Boron from p-Boronophenylalanine in Surgically Acquired Samples of Human Brain Tumor Tissue. .. 899

Duane R. Smith, Subhash Chandra, Jeffrey A. Coderre, Darrel D. Joel, Daniel N. Slatkin, Arjun D. Chanana, Eric H. Elowitz, Marta M. Nawrocky, Peggy L. Micca, and George H. Morrison

136. In Vitro Exposure of Human T98G Glioblastoma Cells to Mixed BNCT Drugs: Acquiring Independent Quantitative Images of Boron Atoms Delivered by IOBPA_F and "BSH in the Same Cell by SIMS Ion Microscopy . . . . . . . . . . . . . . . . . . . . . . . .. 905

Subhash Chandra, Daniel R. Lorey II, Duane R. Smith, and George H. Morrison

Contents xxxiii

128. Structure Determination of p-Boronophenylalanine-Fructose Complex Using llcc Coupling Constants. . . . . . . . . . . . . . . .. 857

Miyuki Kitazawa and Kazuo Yoshino

129. Simultaneous Determination of p-Boronophenylalanine and Boric Acid Using "B-NMR ................................ 863

Kazuo Yoshino, Yasuhito Tanaka, Hidetake Kakihana, Masamitsu Ichihashi, and Yutaka Mishima

130. Structure of the BPA-Fructose Complex: A C-13 NMR Investigation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 869

P. Bendel, C. Anderson, and G. W Kabalka

131. Proton MR Spectroscopic Measurement of p-Boronophenylalanine for in Vivo Pharmacokinetic Studies: A Preliminary Study. . . .. 875

C. S. Zuo, P. V. Prasad, L. Tang, N. Adnani, and R. G. Zamenhof

132. Subcellular Localization of BSH-Containing and Non-BoronContaining Chlorin Derivatives in Living Cells Using Confocal Laser Scanning Microscopy. . . . . . . . . . . . . . . . . . .. 883

Stefanie Steen-Ecke, Franz-Peter Montforts, and Detlef Gabel

133. Quantitative Analysis of Boron in Co-Cultures of Human Glioblastoma T98G Cells and Normal Cell Lines within the Same Field of View of Ion Microscopy Imaging. . . . . . . . . . .. 887

Daniel R. Lorey II, Subhash Chandra, Duane R. Smith, and George H. Morrison

134. Ion Microscopy Imaging of Boron in Animal Tissue Sections for Neutron Capture Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . .. 893

Duane R. Smith, Darrel D. Joel, Jeffrey A. Coderre, Gerard M. Morris, Subhash Chandra, Marta M. Nawrocky, Peggy L. Micca, Hemant Patel, and George H. Morrison

135. Ion Microscopy Imaging of Boron from p-Boronophenylalanine in Surgically Acquired Samples of Human Brain Tumor Tissue. .. 899

Duane R. Smith, Subhash Chandra, Jeffrey A. Coderre, Darrel D. Joel, Daniel N. Slatkin, Arjun D. Chanana, Eric H. Elowitz, Marta M. Nawrocky, Peggy L. Micca, and George H. Morrison

136. In Vitro Exposure of Human T98G Glioblastoma Cells to Mixed BNCT Drugs: Acquiring Independent Quantitative Images of Boron Atoms Delivered by IOBPA_F and "BSH in the Same Cell by SIMS Ion Microscopy . . . . . . . . . . . . . . . . . . . . . . . .. 905

Subhash Chandra, Daniel R. Lorey II, Duane R. Smith, and George H. Morrison

xxxiv Contents

l37. A Combination of Immunohistochemistry and Photoelectron Spectromicroscopy for Investigations of Subcellular Boron Distribution. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 911

Michael Neumann, Ge1somina De Stasio, Benjamin Gilbert, Jose Redondo, and Detlef Gabel

l38. A Method for Determining the Concentration of Boron in Blood by the Measurement of Thermal Neutron Flux Depression. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 917

S. L. Brooke, S. Green, and D. R. Weaver

l39. Non-Invasive Quantification of Gadolinium Uptake in Tumors. . . .. 923 M. A. Meyer, R. M. Brugger, 1. C. Lattimer, K. Kutikkad,

A. R. Schoone, and G. Ehrhardt

140. Subcellular Biodistribution of Na2B12HllSH (BSH) in Rat Glioma Model. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 927

Teruyoshi Kageji, Shinji Nagahiro, Keizo Matsumoto, Birte Otersen, Detlef Gabel, Manekazu Nakaichi, and Yoshinobu Nakagawa

141. Determination of BSH (Na2B12HllSH) Absorbed in Tumor Tissue. .. 933 Yoshinobu Nakagawa, Kyonghon Pooh, Michiko Sone,

Teruyoshi Kageji, M. Nakaichi, Hiroshi Takahashi, K. Amemiya, and Detlef Gabel

142. Detection of lOB Distributions in Histological Samples by Neutron Capture Autoradiography Using Cold Neutron Beams and Photoluminescent Imaging Plates . . . . . . . . . . . . . . . . . . . . . .. 939

1. Rant, M. Cemazar, G. Bayon, Y. Yanagie, 1. Skrk, H. Kobayashi, D. Gabel, and G. Sersa

143. Alpha-Autoradiographic Determination of lOB Concentrations in Cancer Bearing Mice for Boron Neutron-Capture Therapy. . .. 945

Hironobu Yanagie, Koichi Ogura, Yasumasa Nonaka, Toshio Matumoto, Yoshinori Sakurai, Tooru Kobayashi, Kouji Ono, Masazumi Eriguchi, and Hisao Kobayashi

PHARMACOLOGY AND COMPOUND EVALUATION

144. A New Simplified System for the Evaluation of BNCT Pharmaceuticals. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 955

T. E. Byrne, L. F. Miller, G. W. Kabalka, and R. C. Martin

145. Compartmental and Non-Compartmental Methods in Studying the Kinetics of Boron-lO after Boronophenylalanine Fructose Complex (BPA-F)-Infusion in Dogs. . . . . . . . . . . . . . . . . . . .. 959

Paivi Ryynanen, Sauli Savolainen, Judit Benczik, Martti Kulvik, Jyrki Vahatalo, and Marjatta Snellman

xxxiv Contents

l37. A Combination of Immunohistochemistry and Photoelectron Spectromicroscopy for Investigations of Subcellular Boron Distribution. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 911

Michael Neumann, Ge1somina De Stasio, Benjamin Gilbert, Jose Redondo, and Detlef Gabel

l38. A Method for Determining the Concentration of Boron in Blood by the Measurement of Thermal Neutron Flux Depression. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 917

S. L. Brooke, S. Green, and D. R. Weaver

l39. Non-Invasive Quantification of Gadolinium Uptake in Tumors. . . .. 923 M. A. Meyer, R. M. Brugger, 1. C. Lattimer, K. Kutikkad,

A. R. Schoone, and G. Ehrhardt

140. Subcellular Biodistribution of Na2B12HllSH (BSH) in Rat Glioma Model. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 927

Teruyoshi Kageji, Shinji Nagahiro, Keizo Matsumoto, Birte Otersen, Detlef Gabel, Manekazu Nakaichi, and Yoshinobu Nakagawa

141. Determination of BSH (Na2B12HllSH) Absorbed in Tumor Tissue. .. 933 Yoshinobu Nakagawa, Kyonghon Pooh, Michiko Sone,

Teruyoshi Kageji, M. Nakaichi, Hiroshi Takahashi, K. Amemiya, and Detlef Gabel

142. Detection of lOB Distributions in Histological Samples by Neutron Capture Autoradiography Using Cold Neutron Beams and Photoluminescent Imaging Plates . . . . . . . . . . . . . . . . . . . . . .. 939

1. Rant, M. Cemazar, G. Bayon, Y. Yanagie, 1. Skrk, H. Kobayashi, D. Gabel, and G. Sersa

143. Alpha-Autoradiographic Determination of lOB Concentrations in Cancer Bearing Mice for Boron Neutron-Capture Therapy. . .. 945

Hironobu Yanagie, Koichi Ogura, Yasumasa Nonaka, Toshio Matumoto, Yoshinori Sakurai, Tooru Kobayashi, Kouji Ono, Masazumi Eriguchi, and Hisao Kobayashi

PHARMACOLOGY AND COMPOUND EVALUATION

144. A New Simplified System for the Evaluation of BNCT Pharmaceuticals. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 955

T. E. Byrne, L. F. Miller, G. W. Kabalka, and R. C. Martin

145. Compartmental and Non-Compartmental Methods in Studying the Kinetics of Boron-lO after Boronophenylalanine Fructose Complex (BPA-F)-Infusion in Dogs. . . . . . . . . . . . . . . . . . . .. 959

Paivi Ryynanen, Sauli Savolainen, Judit Benczik, Martti Kulvik, Jyrki Vahatalo, and Marjatta Snellman

Contents

146. Time-Dependent Biodistribution of BPA-F in Normal and Tumor Brain Tissues in Mice. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 965

Cynthia Chuang, Matthew Palmer, Robert Zamenhof, and Paul Busse

147. Boron-lO Distribution of p-Boronophenylalanine in the Experimental Brain Tumor in the Rats. . . . . . . . . . . . . . . . . .. 973

Munekazu Nakaichi, Yuko Hori, Toshinari Hasegawa, Sanenori Nakama, Akira Takeuchi, and Yoshinobu Nakagawa

148. BPA Uptake and Efflux through the Cellular Membrane. . . . . . . . .. 979 A. Wittig, W A. Sauerwein, and J. A. Coderre

149. A Further Mechanism Study of Boron Accumulation to and Release from Melanoma with p-Boronophenylalanine . . . . . . .. 985

Kazuo Yoshino, Mamiko Kamijo, Mototetsu Kimura, Yutaka Mishima, Hirofumi Kondoh, Mitsutaka Kadota, Syosuke Ito, Kazumasa Wakamatsu, and Hidetake Kakihana

ISO. Enhanced Uptake of Boronophenylalanine and Efficacy of BNCT in F98 Glioma Bearing Rats Following Administration of Cereport TM. . • . . . . . . . . . . . . . . . . . . . . . . . . • . . . . . . . . . • .. 991

Weilian Yang, Rolf F. Barth, Joan H. Rotaru, Jeffrey A. Coderre, Marta M. Nawrocky, and Raymond T. Bartus

lSI. Effect of Dose and Infusion Time on the Delivery of pBoronophenylalanine for Neutron Capture Therapy. . . . . . . .. 997

Darrel D. Joel, Jeffrey A. Coderre, Peggy L. Micca, and Marta M. Nawrocky

152. In Vitro Uptake Study of 5-Carboranyl Uridine and Its Derivatives. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1003

Toshinari Hasegawa, Munekazu Nakaichi, Sanenori Nakama, Hiroyuki Nakamura, Yoshinori Yamamoto, Masao Takagaki, and Akira Takeuchi

153. Evaluation of Carboranyl 2'-Deoxyuridine Derivatives as Substrates for Human Thymidine Kinases 1 and 2 ................... 1009

Jianghai Wang, Anthony J. Lunato, Abul K. M. Anisuzzaman, Seiichiro Ikeda, Weihua Ji, Feng-Guang Rong, Staffan Eriksson, David H. Ives, Albert H. Soloway, and Werner Tjarks

154. In Vivo and In Vitro Uptake Study of Boronated Porphyrins for Neutron Capture Therapy ............................ lOIS

Akira Matsumura, Yasushi Shibata, Tetsuya Yamamoto, Fumiyo Yoshida, Kei Nakai, Isao Sakata, Susumu Nakajima, Masafumi Okumura, and Tadao Nose

xxxv Contents

146. Time-Dependent Biodistribution of BPA-F in Normal and Tumor Brain Tissues in Mice. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 965

Cynthia Chuang, Matthew Palmer, Robert Zamenhof, and Paul Busse

147. Boron-lO Distribution of p-Boronophenylalanine in the Experimental Brain Tumor in the Rats. . . . . . . . . . . . . . . . . .. 973

Munekazu Nakaichi, Yuko Hori, Toshinari Hasegawa, Sanenori Nakama, Akira Takeuchi, and Yoshinobu Nakagawa

148. BPA Uptake and Efflux through the Cellular Membrane. . . . . . . . .. 979 A. Wittig, W A. Sauerwein, and J. A. Coderre

149. A Further Mechanism Study of Boron Accumulation to and Release from Melanoma with p-Boronophenylalanine . . . . . . .. 985

Kazuo Yoshino, Mamiko Kamijo, Mototetsu Kimura, Yutaka Mishima, Hirofumi Kondoh, Mitsutaka Kadota, Syosuke Ito, Kazumasa Wakamatsu, and Hidetake Kakihana

ISO. Enhanced Uptake of Boronophenylalanine and Efficacy of BNCT in F98 Glioma Bearing Rats Following Administration of Cereport TM. . • . . . . . . . . . . . . . . . . . . . . . . . . • . . . . . . . . . • .. 991

Weilian Yang, Rolf F. Barth, Joan H. Rotaru, Jeffrey A. Coderre, Marta M. Nawrocky, and Raymond T. Bartus

lSI. Effect of Dose and Infusion Time on the Delivery of pBoronophenylalanine for Neutron Capture Therapy. . . . . . . .. 997

Darrel D. Joel, Jeffrey A. Coderre, Peggy L. Micca, and Marta M. Nawrocky

152. In Vitro Uptake Study of 5-Carboranyl Uridine and Its Derivatives. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1003

Toshinari Hasegawa, Munekazu Nakaichi, Sanenori Nakama, Hiroyuki Nakamura, Yoshinori Yamamoto, Masao Takagaki, and Akira Takeuchi

153. Evaluation of Carboranyl 2'-Deoxyuridine Derivatives as Substrates for Human Thymidine Kinases 1 and 2 ................... 1009

Jianghai Wang, Anthony J. Lunato, Abul K. M. Anisuzzaman, Seiichiro Ikeda, Weihua Ji, Feng-Guang Rong, Staffan Eriksson, David H. Ives, Albert H. Soloway, and Werner Tjarks

154. In Vivo and In Vitro Uptake Study of Boronated Porphyrins for Neutron Capture Therapy ............................ lOIS

Akira Matsumura, Yasushi Shibata, Tetsuya Yamamoto, Fumiyo Yoshida, Kei Nakai, Isao Sakata, Susumu Nakajima, Masafumi Okumura, and Tadao Nose

xxxv

xxxvi Contents

155. Toxicology of BOPP in Large Animals ....................... 1021 Jay Tibbitts, John R. Fike, Kathleen R. Lamborn,

Andrew W Bollen, and Stephen B. Kahl

156. Biodistribution Study of Novel Dodecaborate-Phthalocyanines in the B-16 Mouse Melanoma Model ...................... 1027

R. Spryshkova, E. Grigorieva, V. Riabkova, Zh. Spure, M. Naidenov, K. Zhizhin, E. Malinina, A. Chernyavsky, E. Luk'yanets, K. Solntsev, N. Kuznetsov, and G. Borisov

157. Investigations of the Interaction of Phospholipids with Mercaptoundecahydro-closo-Dodecaborate (2-) (BSH) and Dodecahydro-closo-Dodecaborate (2-) (B12H 122-) •••••••••••• 1033

Silke Lutz and Detlef Gabel

158. Membrane Binding of Na2B12HllSH (BSH) with Phosphatidylcholine in Boron Neutron Capture Therapy. . . . . . 1039

Teruyoshi Kageji, Shinji Nagahiro, Keizo Matsumoto, Birte Otersen, Detlef Gabel, and Yoshinobu Nakagawa

159. Investigation of the Toxicity and Cellular Uptake of Na4[B20H17SH] in EMT6 Tumor Cells ............................... 1045

R. Corey Waller, Debra A. Feakes, Jennifer SpinIer, Greg Southard, and Gary M. Aron

160. Evaluation of the Binding of Polyhedral Borane Compounds to Intracellular Protein Moieties and Monomeric Amino Acids ... 1051

R. Corey Waller, Jennifer SpinIer, and Debra A. Feakes

161. Cremophor EL Alters Uptake, Retention, Distribution, and Toxicity of the Boron Containing Ether Lipid rac-1-(9-o-Carboranyl)Nonyl-2-Methyl-Glycero-3-Phosphocholine (B-Et-ll-OMe) ..................................... 1057

Peter Lemmen, Lothar WeiBfloch, Thomas Probst, Peter Luppa, Peggy L. Micca, and Michiko Miura

162. Analysis of in Vivo Uptake for Boron Neutron Capture Synovectomy ...................................... 1063

E. Binello, S. Shortkroff, R. E. Shefer, A. G. Jones, A. Davison, T. Thornhill, and 1. C. Yanch

TISSUE TARGETING

163. SLT-Particles for Two-Step Targeting in Boron Neutron Capture Therapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1069

E. Boh1, 1. Carlsson, K. Edwards, S. Sjoberg, and L. Gedda

xxxvi Contents

155. Toxicology of BOPP in Large Animals ....................... 1021 Jay Tibbitts, John R. Fike, Kathleen R. Lamborn,

Andrew W Bollen, and Stephen B. Kahl

156. Biodistribution Study of Novel Dodecaborate-Phthalocyanines in the B-16 Mouse Melanoma Model ...................... 1027

R. Spryshkova, E. Grigorieva, V. Riabkova, Zh. Spure, M. Naidenov, K. Zhizhin, E. Malinina, A. Chernyavsky, E. Luk'yanets, K. Solntsev, N. Kuznetsov, and G. Borisov

157. Investigations of the Interaction of Phospholipids with Mercaptoundecahydro-closo-Dodecaborate (2-) (BSH) and Dodecahydro-closo-Dodecaborate (2-) (B12H 122-) •••••••••••• 1033

Silke Lutz and Detlef Gabel

158. Membrane Binding of Na2B12HllSH (BSH) with Phosphatidylcholine in Boron Neutron Capture Therapy. . . . . . 1039

Teruyoshi Kageji, Shinji Nagahiro, Keizo Matsumoto, Birte Otersen, Detlef Gabel, and Yoshinobu Nakagawa

159. Investigation of the Toxicity and Cellular Uptake of Na4[B20H17SH] in EMT6 Tumor Cells ............................... 1045

R. Corey Waller, Debra A. Feakes, Jennifer SpinIer, Greg Southard, and Gary M. Aron

160. Evaluation of the Binding of Polyhedral Borane Compounds to Intracellular Protein Moieties and Monomeric Amino Acids ... 1051

R. Corey Waller, Jennifer SpinIer, and Debra A. Feakes

161. Cremophor EL Alters Uptake, Retention, Distribution, and Toxicity of the Boron Containing Ether Lipid rac-1-(9-o-Carboranyl)Nonyl-2-Methyl-Glycero-3-Phosphocholine (B-Et-ll-OMe) ..................................... 1057

Peter Lemmen, Lothar WeiBfloch, Thomas Probst, Peter Luppa, Peggy L. Micca, and Michiko Miura

162. Analysis of in Vivo Uptake for Boron Neutron Capture Synovectomy ...................................... 1063

E. Binello, S. Shortkroff, R. E. Shefer, A. G. Jones, A. Davison, T. Thornhill, and 1. C. Yanch

TISSUE TARGETING

163. SLT-Particles for Two-Step Targeting in Boron Neutron Capture Therapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1069

E. Boh1, 1. Carlsson, K. Edwards, S. Sjoberg, and L. Gedda

Contents

164. Application of lOB Entrapped Liposome to Boron Neutron Capture Therapy for Pancreatic Cancer Model in Vivo . . . . . . . . . . . . . . 1077

Hironobu Yanagie, Koichi Ogura, Kazuo Maruyama, Yasumasa Nonaka, Toshio Matumoto, Yoshinori Sakurai, Tooru Kobayashi, Kouji Ono, Masazumi Eriguchi, and Hisao Kobayashi

165. LDL Receptor Status of Human Glioblastoma Cells ............. 1085 E. A. Blakely, K. A. Bjornstad, L. Maletinska, D. E. Callahan,

L. J. Knoff, D. F. Deen, and T. M. Forte

166. The Advantage of Porphyrin for BNCT from the Point of View of Cell Cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1089

Yasushi Shibata, Akira Matsumura, Fumiyo Yoshida, Tetsuya Yamamoto, Kei Nakai, Tadao Nose, Isao Sakata, and Susumu Nakajima

167. Strategies to Improve the Efficacy of Neutron Capture Therapy of Brain Tumors by Optimizing Delivery of Boron Compounds .. 1093

Rolf F. Barth, Weilian Yang, and Albert H. Soloway

168. Boron-Rich Oligomeric Phosphate Diesters that Target the Cell Nucleus in Vitro . ................................... 1103

Mark B. Smuckler, Lufeng Guan, Akira Nakanishi, Harumi Kasamatsu, and M. Frederick Hawthorne

169. Biodistribution of Technetium-99m Labeled Epidermal Growth Factor Following Intracarotid Injection into Rats Bearing Intracerebral EGF Receptor (+) Gliomas ................. 1109

Weilian Yang, Rolf F. Barth, Dianne M. Adams, Renee Leveille, and Jacek Capala

170. Biological Evaluation of Boronated Polyamines as Potential Agents for BNCT ........................................ 1115

Jin-Cong Zhuo, Jianping Cai, Albert H. Soloway, Rolf F. Barth, Dianne M. Adams, Weihua Ji, Werner Tjarks, and Joan H. Rotaru

171. Preclinical Development of P-D-5-o-Carboranyl-2'-Deoxyuridine (D-CDU) for the Treatment of Malignant Brain Tumors ...... 1121

Raymond F. Schinazi, Selwyn J. Hurwitz, Irina Liberman, Amy Juodawlkis, Junxing Shi, Dennis C. Liotta, Jeffrey Coderre, and Jeffrey Olson

172. Selective Tumor Uptake of Boronopheny1a1anine-Fructose (BPA-F) in an Animal Model of Hepatic Colorectal Metastases ....... 1125

Cynthia Chuang, Paul Busse, Matthew Palmer, Peter Thomas, and Robert Zamenhof

xxxvii Contents

164. Application of lOB Entrapped Liposome to Boron Neutron Capture Therapy for Pancreatic Cancer Model in Vivo . . . . . . . . . . . . . . 1077

Hironobu Yanagie, Koichi Ogura, Kazuo Maruyama, Yasumasa Nonaka, Toshio Matumoto, Yoshinori Sakurai, Tooru Kobayashi, Kouji Ono, Masazumi Eriguchi, and Hisao Kobayashi

165. LDL Receptor Status of Human Glioblastoma Cells ............. 1085 E. A. Blakely, K. A. Bjornstad, L. Maletinska, D. E. Callahan,

L. J. Knoff, D. F. Deen, and T. M. Forte

166. The Advantage of Porphyrin for BNCT from the Point of View of Cell Cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1089


167. Strategies to Improve the Efficacy of Neutron Capture Therapy of Brain Tumors by Optimizing Delivery of Boron Compounds .. 1093

Rolf F. Barth, Weilian Yang, and Albert H. Soloway

168. Boron-Rich Oligomeric Phosphate Diesters that Target the Cell Nucleus in Vitro . ................................... 1103

Mark B. Smuckler, Lufeng Guan, Akira Nakanishi, Harumi Kasamatsu, and M. Frederick Hawthorne

169. Biodistribution of Technetium-99m Labeled Epidermal Growth Factor Following Intracarotid Injection into Rats Bearing Intracerebral EGF Receptor (+) Gliomas ................. 1109

Weilian Yang, Rolf F. Barth, Dianne M. Adams, Renee Leveille, and Jacek Capala

170. Biological Evaluation of Boronated Polyamines as Potential Agents for BNCT ........................................ 1115

Jin-Cong Zhuo, Jianping Cai, Albert H. Soloway, Rolf F. Barth, Dianne M. Adams, Weihua Ji, Werner Tjarks, and Joan H. Rotaru

171. Preclinical Development of P-D-5-o-Carboranyl-2'-Deoxyuridine (D-CDU) for the Treatment of Malignant Brain Tumors ...... 1121

Raymond F. Schinazi, Selwyn J. Hurwitz, Irina Liberman, Amy Juodawlkis, Junxing Shi, Dennis C. Liotta, Jeffrey Coderre, and Jeffrey Olson

172. Selective Tumor Uptake of Boronopheny1a1anine-Fructose (BPA-F) in an Animal Model of Hepatic Colorectal Metastases ....... 1125

Cynthia Chuang, Paul Busse, Matthew Palmer, Peter Thomas, and Robert Zamenhof

xxxvii

xxxviii

PRECLINICAL DOSIMETRY

173. BNCT Microdosimetry of a Rat Glioma Model with BPA-F or BSH .......................................... 1133

W S. Kiger III, H. Patel, and R. G. Zamenhof

174. Determination of the Compound Factors of BSH and BPA for Glial Progenitor Survival in a Small Animal Model Using Thermal and Epithermal Neutron Irradiation .............. 1139

H. Philippo, E. A. M. Winter-van Kampen, S. Spanjer, R. Huiskamp, and A. J. van der Kogel

175. Analytical Evaluating Method of lOB(n,<xy)7Li Prompt Gamma-Ray Spectrum for Measuring Absorbed Dose Distribution in Boron Neutron Capture Therapy ....................... 1145

Masayori Ishikawa, Tooru Kobayashi, and Keiji Kanda

176. Modeling the Impact of Near-Threshold 7Li(p,n) 7Be Generated, Fast Neutron Beams on Boron Drug Distribution Requirements for BNCT .............................. 1151

T. R. LaHann, M. Griebenow, and J. Larsen

177. Computational Dosimetry for Boron Neutron Capture Synovectomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1159

D. W Nigg, C. A. Wemple, F. J. Wheeler, D. E. Wessol, J. C. Yanch, and C. D. Scoville

178. Application of Thermoluminescent Dosimeters to Mixed Neutron-Gamma Dosimetry for BNCT ......................... 1165

C. Kessler, F. Stecher-Rasmussen, J. Rassow, S. Garbe, and W Sauerwein

179. Semiconductor Detectors for In-Phantom Thermal Neutron Flux and Boron Dose Measurements in BNCT and Fast Neutron Therapy ................................... 1175

Greg 1. Kaplan, Anato1y B. Rosenfeld, Barry J. Allen, Jeffrey A. Coderre, Tooru Kobayashi, Richard L. Maughan, Chandrasekhar Kota, Mark Yudelev, Vladimir 1. Khivrich, and Petro G. Litovchenko

180. Determination of an RBE for an Epithermal Neutron Beam for BNCT from Microdosimetric Measurements ............... 1181

Stuart Green, Mark Gainey, and Cecile Wojnecki

181. Effects of Neutron Collimation, Beam Size, and Spectrum on InPhantom Performance of Realistic Epithermal Neutron Beams for BNCT ................................... 1187

W S. Kiger III, S. Sakamoto, and O. K. Harling

Contents xxxviii

PRECLINICAL DOSIMETRY

173. BNCT Microdosimetry of a Rat Glioma Model with BPA-F or BSH .......................................... 1133

W S. Kiger III, H. Patel, and R. G. Zamenhof

174. Determination of the Compound Factors of BSH and BPA for Glial Progenitor Survival in a Small Animal Model Using Thermal and Epithermal Neutron Irradiation .............. 1139

H. Philippo, E. A. M. Winter-van Kampen, S. Spanjer, R. Huiskamp, and A. J. van der Kogel

175. Analytical Evaluating Method of lOB(n,<xy)7Li Prompt Gamma-Ray Spectrum for Measuring Absorbed Dose Distribution in Boron Neutron Capture Therapy ....................... 1145

Masayori Ishikawa, Tooru Kobayashi, and Keiji Kanda

176. Modeling the Impact of Near-Threshold 7Li(p,n) 7Be Generated, Fast Neutron Beams on Boron Drug Distribution Requirements for BNCT .............................. 1151

T. R. LaHann, M. Griebenow, and J. Larsen

177. Computational Dosimetry for Boron Neutron Capture Synovectomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1159

D. W Nigg, C. A. Wemple, F. J. Wheeler, D. E. Wessol, J. C. Yanch, and C. D. Scoville

178. Application of Thermoluminescent Dosimeters to Mixed Neutron-Gamma Dosimetry for BNCT ......................... 1165

C. Kessler, F. Stecher-Rasmussen, J. Rassow, S. Garbe, and W Sauerwein

179. Semiconductor Detectors for In-Phantom Thermal Neutron Flux and Boron Dose Measurements in BNCT and Fast Neutron Therapy ................................... 1175

Greg 1. Kaplan, Anato1y B. Rosenfeld, Barry J. Allen, Jeffrey A. Coderre, Tooru Kobayashi, Richard L. Maughan, Chandrasekhar Kota, Mark Yudelev, Vladimir 1. Khivrich, and Petro G. Litovchenko

180. Determination of an RBE for an Epithermal Neutron Beam for BNCT from Microdosimetric Measurements ............... 1181

Stuart Green, Mark Gainey, and Cecile Wojnecki

181. Effects of Neutron Collimation, Beam Size, and Spectrum on InPhantom Performance of Realistic Epithermal Neutron Beams for BNCT ................................... 1187

W S. Kiger III, S. Sakamoto, and O. K. Harling

Contents

Contents

182. Dose Distribution in 157Gd and lOB Containing Phantoms Subsequent to Irradiation with Thermal Neutrons .......... 1195

V. F. Khokhlov, A. I. Shaks, V. L. Gozenbuk, I. N. Sheino, V. L. Mazanov, K. N. Zaitsev, V. K. Sakharov, and R. Lawaczeck

183. 252Cf Mixed-Field Dosimetry for a Variety of Source Geometries and Phantom Materials for Clinical Brachytherapy: Comparison of Measurements and Calculations ............ 1203

Mark 1. Rivard, Mark Yudelev, Frank Van den Heuvel, Jacek G. Wierzbicki, Rodger C. Martin, and Robert R. McMahon

184. 157Gd Photon Dose Enhancement from a Neutron Emitting 252Cf Point Source ...................................... 1211

Mark 1. Rivard, Mark Yudelev, and Jacek G. Wierzbicki

185. Theoretical Cell Survival Probability for Preclinical Evaluation of BNCT Treatment Conditions .......................... 1219

Sung-Joon Ye and Karl O. Ott

186. A Monte Carlo Calculation of the Change in Dosimetric Properties on the Usage of Heavy Water for Boron Neutron Capture Therapy .......................................... 1225

Wanno Lee, Eun-Hee Kim, Gyuseoung Cho, and Seung-Hoon Lee

PRECLINICAL RADIOBIOLOGY

187. Large Animal Model for Healthy Tissue Tolerance Study in BNCT ........................................... 1233

J. Benczik, T. Seppala, J. Hopewell, M. Snellman, I. Auterinen, R. Joensuu, U. Abo Ramadan, J. Tanttu, J. Vahiitalo, M. Kulvik, H. Joensuu, M. Tenhunen, S. Savolainen, M. Kallio, and M. Farkkila

188. A Large Animal Model Study Investigating Potential BNCT Retreatment Using BSH .............................. 1239

Patrick R. Gavin, Hege Kippenes, and Judit Benczik

189. Dosimetry Chain for the Dogs Irradiated in the Epithermal Neutron Beam at the Finnish BNCT Facility ..................... 1245

Sauli Savolainen, Iiro Auterinen, Carita Aschan, Pekka Hiismaki, Mika Kortesniemi, Antti Kosunen, Petri Kotiluoto, Juha Lampinen, Tiina Seppala, Tom Seren, Vesa Tanner, and Matti Toivonen

190. In Vivo Dosimetry of the Dog Irradiations at the Finnish BNCT Facility .......................................... 1251

Carita Aschan, Tom Seren, Tiina Seppala, Judit Benczik, Matti Toivonen, liro Auterinen, and Sauli Savolainen

xxxix Contents

182. Dose Distribution in 157Gd and lOB Containing Phantoms Subsequent to Irradiation with Thermal Neutrons .......... 1195

V. F. Khokhlov, A. I. Shaks, V. L. Gozenbuk, I. N. Sheino, V. L. Mazanov, K. N. Zaitsev, V. K. Sakharov, and R. Lawaczeck

183. 252Cf Mixed-Field Dosimetry for a Variety of Source Geometries and Phantom Materials for Clinical Brachytherapy: Comparison of Measurements and Calculations ............ 1203

Mark 1. Rivard, Mark Yudelev, Frank Van den Heuvel, Jacek G. Wierzbicki, Rodger C. Martin, and Robert R. McMahon

184. 157Gd Photon Dose Enhancement from a Neutron Emitting 252Cf Point Source ...................................... 1211

Mark 1. Rivard, Mark Yudelev, and Jacek G. Wierzbicki

185. Theoretical Cell Survival Probability for Preclinical Evaluation of BNCT Treatment Conditions .......................... 1219

Sung-Joon Ye and Karl O. Ott

186. A Monte Carlo Calculation of the Change in Dosimetric Properties on the Usage of Heavy Water for Boron Neutron Capture Therapy .......................................... 1225

Wanno Lee, Eun-Hee Kim, Gyuseoung Cho, and Seung-Hoon Lee

PRECLINICAL RADIOBIOLOGY

187. Large Animal Model for Healthy Tissue Tolerance Study in BNCT ........................................... 1233

J. Benczik, T. Seppala, J. Hopewell, M. Snellman, I. Auterinen, R. Joensuu, U. Abo Ramadan, J. Tanttu, J. Vahiitalo, M. Kulvik, H. Joensuu, M. Tenhunen, S. Savolainen, M. Kallio, and M. Farkkila

188. A Large Animal Model Study Investigating Potential BNCT Retreatment Using BSH .............................. 1239

Patrick R. Gavin, Hege Kippenes, and Judit Benczik

189. Dosimetry Chain for the Dogs Irradiated in the Epithermal Neutron Beam at the Finnish BNCT Facility ..................... 1245

Sauli Savolainen, Iiro Auterinen, Carita Aschan, Pekka Hiismaki, Mika Kortesniemi, Antti Kosunen, Petri Kotiluoto, Juha Lampinen, Tiina Seppala, Tom Seren, Vesa Tanner, and Matti Toivonen

190. In Vivo Dosimetry of the Dog Irradiations at the Finnish BNCT Facility .......................................... 1251

Carita Aschan, Tom Seren, Tiina Seppala, Judit Benczik, Matti Toivonen, liro Auterinen, and Sauli Savolainen

xxxix

xl Contents

191. Survival after BNCT in Combination with Surgery for Dogs with Spontaneous Brain Tumors ........................... 1257

Rodney S. Bagley, Patrick R. Gavin, Michael P. Boore, Gena M. Silver, Michael L. Harrington, and Hege Kippenes

192. Quantitative MRI in Assessing Irradiation Effect in Dog Brain ..... 1263 U. Abo Ramadan, J. Benczik, H. Joensuu, R. Joensuu,

M. Kallio, L. Kankaanranta, S. Savolainen, M. Snellman, J. Tanttu, and M. Tenhunen

193. Irradiation of Dog Brain with Single Doses of X-Rays ........... 1269 J. Benczik, M. Tenhunen, J. Hopewell, M. Snellman, M. Kallio,

L. Kankaanranta, and H. Joensuu

194. A Rat Model of Oral Mucosal Response to Boron Neutron Capture Irradiation ................................. 1273

G. M. Morris, J. A. Coderre, D. R. Smith, and J. W Hopewell

195. Split-Dose BNCT Irradiations of Rat Oral Mucosa and Rat Brain Tumor Using BPA: Effects on Tolerance and Survival ........ 1279

Jeffrey A. Coderre, Gerard M. Morris, Ruimei Ma, Peggy L. Micca, Diana T. Lombardo, Kellyann M. Youngs, and John Kalef-Ezra

196. Efficacy of Boron Neutron-Capture Therapy Using a CarboraneContaining Tetraphenylporphyrin in Mice Bearing EMT-6 Tumors .......................................... 1285

Michiko Miura, Peggy L. Micca, Diana T. Lombardo, Kelly M. Youngs, Gerard M. Morris, John A. Ka1ef-Ezra, Ruimei Ma, and Jeffrey A. Coderre

197. Apoptosis of Tumor Cells in Response to Boron Neutron Capture Therapy .......................................... 1293

Tetsuya Yamamoto, Akira Matsumura, Yasushi Shibata, Fumiyo Yoshida, Kei Nakai, Tadao Nose, Youji Horiguchi, Masao Aizawa, Susumu Nakajima, and Isao Sakata

198. Apoptosis Induced by Boron Neutron Capture Therapy for Brain Tumors .......................................... 1299

Michael A. Domet, Birte Otersen, Rolf F. Barth, Weilian Yang, Joan Rotaru, Zunyan Dai, James R. Lang, and Marta M. Nawrocky

199. Cell Cycle Change of 9L Glioma Cell after in Vitro Boron Neutron Capture Therapy ................................... 1305


xl Contents

191. Survival after BNCT in Combination with Surgery for Dogs with Spontaneous Brain Tumors ........................... 1257

Rodney S. Bagley, Patrick R. Gavin, Michael P. Boore, Gena M. Silver, Michael L. Harrington, and Hege Kippenes

192. Quantitative MRI in Assessing Irradiation Effect in Dog Brain ..... 1263 U. Abo Ramadan, J. Benczik, H. Joensuu, R. Joensuu,

M. Kallio, L. Kankaanranta, S. Savolainen, M. Snellman, J. Tanttu, and M. Tenhunen

193. Irradiation of Dog Brain with Single Doses of X-Rays ........... 1269 J. Benczik, M. Tenhunen, J. Hopewell, M. Snellman, M. Kallio,

L. Kankaanranta, and H. Joensuu

194. A Rat Model of Oral Mucosal Response to Boron Neutron Capture Irradiation ................................. 1273

G. M. Morris, J. A. Coderre, D. R. Smith, and J. W Hopewell

195. Split-Dose BNCT Irradiations of Rat Oral Mucosa and Rat Brain Tumor Using BPA: Effects on Tolerance and Survival ........ 1279

Jeffrey A. Coderre, Gerard M. Morris, Ruimei Ma, Peggy L. Micca, Diana T. Lombardo, Kellyann M. Youngs, and John Kalef-Ezra

196. Efficacy of Boron Neutron-Capture Therapy Using a CarboraneContaining Tetraphenylporphyrin in Mice Bearing EMT-6 Tumors .......................................... 1285

Michiko Miura, Peggy L. Micca, Diana T. Lombardo, Kelly M. Youngs, Gerard M. Morris, John A. Ka1ef-Ezra, Ruimei Ma, and Jeffrey A. Coderre

197. Apoptosis of Tumor Cells in Response to Boron Neutron Capture Therapy .......................................... 1293

Tetsuya Yamamoto, Akira Matsumura, Yasushi Shibata, Fumiyo Yoshida, Kei Nakai, Tadao Nose, Youji Horiguchi, Masao Aizawa, Susumu Nakajima, and Isao Sakata

198. Apoptosis Induced by Boron Neutron Capture Therapy for Brain Tumors .......................................... 1299

Michael A. Domet, Birte Otersen, Rolf F. Barth, Weilian Yang, Joan Rotaru, Zunyan Dai, James R. Lang, and Marta M. Nawrocky

199. Cell Cycle Change of 9L Glioma Cell after in Vitro Boron Neutron Capture Therapy ................................... 1305


Contents

200. Radiobiological Effects of Boronated Porphyrin (STA-BX909) Compared to BSH in Cultured Glioma Cell Line . . . . . . . . . . . 1311

Akira Matsumura, Yasushi Shibata, Tetsuya Yamamoto, Fumiyo Yoshida, Yoshinori Hayakawa, Tomonori Isobe, Kei Nakai, Isao Sakata, Susumu Nakajima, Naoto Miwa, Koji Ono, and Tadao Nose

201. Mutagenic Effects at HPRT Locus in Chinese Hamster Ovary (CHO) Cells Induced by Epi-Therma1 and Thermal Neutrons .................................. l317

Yuko Kinashi, Yoshinori Sakurai, Shinichiro Masunaga, Minoru Suzuki, Masao Takagaki, and Koji Ono

202. Evaluation of Neurotoxicity and Radiation Effects of BNCT in Rats Following Blood-Brain Barrier Disruption and Intracarotid Injection of BPA or BSH ................... 1323

Wei1ian Yang, Rolf F. Barth, Joan H. Rotaru, Jacqueline C. Bresnahan, Maria Hadjiconstantinous, Darrel D. Joel, and Marta M. Nawrocky

203. Cell Survival Following in Vitro Irradiation at Depth in a Lucite Phantom as a Measure of Epithermal Beam RBE ........... 1329

Jeffrey A. Coderre, Jacek Capa1a, Ruimei Ma, and Michael Makar

204. Applicability of Combination with Tirapazamine in Boron Neutron Capture Therapy: Concerning Effectiveness on Quiescent Tumor Cell Populations within Solid Tumors .............. 1335

Shin-ichiro Masunaga, Koji Ono, Yoshinori Sakurai, Hitoshi Hori, Masao Takagaki, Toru Kobayashi, Minoru Suzuki, Yuko Kinashi, and Mitsuhiko Akaboshi

205. Behaviors of Cells in Different Proliferative States within Solid Tumors in Boron and Gadolinium Neutron Capture Therapy When Irradiated with Two Different Cadmium Ratio Neutrons .................................... 1343

Shin-ichiro Masunaga, Koji Ono, Yoshinori Sakurai, Minoru Suzuki, Masao Takagaki, Toru Kobayashi, Yuko Kinashi and Mitsuhiko Akaboshi

206. Depth-Dose Evaluation for Liver Cancer Treatment by BNCT and GdNCT Using an Epithermal Neutron Beam .............. l351

Tetsuo Matsumoto

207. A Compact Cell Culture Disc for Neutron Capture Radiography .... l357 G. Kiihne, N. E. A. Crompton, C. Higgs, H. Reist,

E. Lehmann, 1. Stepanek, T. Suda, H. Blattmann, and B. Larsson

xli Contents

200. Radiobiological Effects of Boronated Porphyrin (STA-BX909) Compared to BSH in Cultured Glioma Cell Line . . . . . . . . . . . 1311

Akira Matsumura, Yasushi Shibata, Tetsuya Yamamoto, Fumiyo Yoshida, Yoshinori Hayakawa, Tomonori Isobe, Kei Nakai, Isao Sakata, Susumu Nakajima, Naoto Miwa, Koji Ono, and Tadao Nose

201. Mutagenic Effects at HPRT Locus in Chinese Hamster Ovary (CHO) Cells Induced by Epi-Therma1 and Thermal Neutrons .................................. l317

Yuko Kinashi, Yoshinori Sakurai, Shinichiro Masunaga, Minoru Suzuki, Masao Takagaki, and Koji Ono

202. Evaluation of Neurotoxicity and Radiation Effects of BNCT in Rats Following Blood-Brain Barrier Disruption and Intracarotid Injection of BPA or BSH ................... 1323

Wei1ian Yang, Rolf F. Barth, Joan H. Rotaru, Jacqueline C. Bresnahan, Maria Hadjiconstantinous, Darrel D. Joel, and Marta M. Nawrocky

203. Cell Survival Following in Vitro Irradiation at Depth in a Lucite Phantom as a Measure of Epithermal Beam RBE ........... 1329

Jeffrey A. Coderre, Jacek Capa1a, Ruimei Ma, and Michael Makar

204. Applicability of Combination with Tirapazamine in Boron Neutron Capture Therapy: Concerning Effectiveness on Quiescent Tumor Cell Populations within Solid Tumors .............. 1335

Shin-ichiro Masunaga, Koji Ono, Yoshinori Sakurai, Hitoshi Hori, Masao Takagaki, Toru Kobayashi, Minoru Suzuki, Yuko Kinashi, and Mitsuhiko Akaboshi

205. Behaviors of Cells in Different Proliferative States within Solid Tumors in Boron and Gadolinium Neutron Capture Therapy When Irradiated with Two Different Cadmium Ratio Neutrons .................................... 1343

Shin-ichiro Masunaga, Koji Ono, Yoshinori Sakurai, Minoru Suzuki, Masao Takagaki, Toru Kobayashi, Yuko Kinashi and Mitsuhiko Akaboshi

206. Depth-Dose Evaluation for Liver Cancer Treatment by BNCT and GdNCT Using an Epithermal Neutron Beam .............. l351

Tetsuo Matsumoto

207. A Compact Cell Culture Disc for Neutron Capture Radiography .... l357 G. Kiihne, N. E. A. Crompton, C. Higgs, H. Reist,

E. Lehmann, 1. Stepanek, T. Suda, H. Blattmann, and B. Larsson

xli

xlii Contents

FUTURE DIRECTIONS AND EMERGING APPLICATIONS

208. Current Clinical Paradigms in Melanoma BNCT: Leading to Cell Modulation Era Teamed with Passive and Active IOB-Biodelivery Systems .............................. 1365

Yutaka Mishima, Hirofumi Kondoh, Kazuo Yoshino, and Junichi Hiratsuka

209. BNCT Beyond Glioma Treatment: Where Are the Problems? ...... 1383 Detlef Gabel

210. Progress in the Development of Boron Neutron Capture Synovectomy for the Treatment of Rheumatoid Arthritis ..... 1389

J. C. Yanch, S. Shortkroff, R. E. Shefer, E. Binello, D. Gierga, A. G. Jones, G. Young, C. Vivieros, and B. Blackburn

211. Which is the Best Nuclide for NCT? ......................... 1399 J. F. Crawford and D. Suwannakachorn

212. NCT with Several Agents ................................. 1405 R. M. Brugger

213. Energy Deposited by Electrons in DNA Following n + Gd Interaction ........................................ 1411

S. Mark, I. Orion, B. Laster, and G. Shani

214. Neutron Capture Therapy (BNCT) and Photodynamic Therapy (PDT) Can Both be Accomplished with a Single Compound: Boronated Protoporphyrin (BOPP) ...................... 1417

N. E. A. Crompton, H. Walt, S. B. Kahl, S. D. Klein, Y. Shi, H. Blattmann, U. Haller, and B. Larsson

215. BNCT for the Prevention of Restenosis Following Angioplasty ..... 1423 J. C. Yanch and D. P. Gierga

216. Operative Modalities and Effects of BNCT on Liver Metastases of Colon Adenocarcinoma: A Microscopical and Ultrastructural Study in the Rat. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1427

T. Pinelli, S. Altieri, F. Fossati, A. Zonta, C. Ferrari, U. Prati, L. Roveda, S. Ngnitejeu Tata, S. Barni, P. Chiari, R. Nano, and D. M. Ferguson

Participants List ............................................ 1441 Author Index, Vol. 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. xliii Keyword Index, Vol. 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xlvii

xlii Contents

FUTURE DIRECTIONS AND EMERGING APPLICATIONS

208. Current Clinical Paradigms in Melanoma BNCT: Leading to Cell Modulation Era Teamed with Passive and Active IOB-Biodelivery Systems .............................. 1365

Yutaka Mishima, Hirofumi Kondoh, Kazuo Yoshino, and Junichi Hiratsuka

209. BNCT Beyond Glioma Treatment: Where Are the Problems? ...... 1383 Detlef Gabel

210. Progress in the Development of Boron Neutron Capture Synovectomy for the Treatment of Rheumatoid Arthritis ..... 1389

J. C. Yanch, S. Shortkroff, R. E. Shefer, E. Binello, D. Gierga, A. G. Jones, G. Young, C. Vivieros, and B. Blackburn

211. Which is the Best Nuclide for NCT? ......................... 1399 J. F. Crawford and D. Suwannakachorn

212. NCT with Several Agents ................................. 1405 R. M. Brugger

213. Energy Deposited by Electrons in DNA Following n + Gd Interaction ........................................ 1411

S. Mark, I. Orion, B. Laster, and G. Shani

214. Neutron Capture Therapy (BNCT) and Photodynamic Therapy (PDT) Can Both be Accomplished with a Single Compound: Boronated Protoporphyrin (BOPP) ...................... 1417

N. E. A. Crompton, H. Walt, S. B. Kahl, S. D. Klein, Y. Shi, H. Blattmann, U. Haller, and B. Larsson

215. BNCT for the Prevention of Restenosis Following Angioplasty ..... 1423 J. C. Yanch and D. P. Gierga

216. Operative Modalities and Effects of BNCT on Liver Metastases of Colon Adenocarcinoma: A Microscopical and Ultrastructural Study in the Rat. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1427

T. Pinelli, S. Altieri, F. Fossati, A. Zonta, C. Ferrari, U. Prati, L. Roveda, S. Ngnitejeu Tata, S. Barni, P. Chiari, R. Nano, and D. M. Ferguson

Participants List ............................................ 1441 Author Index, Vol. 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. xliii Keyword Index, Vol. 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xlvii

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Frontiers in Neutron Capture Therapy - Springer978-1-4615-1285-1/1.pdf · Frontiers in neutron capture therapy/edited by M. Frederick Hawthorne, Kenneth Shelly, and Richard J. Wiersema