University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Doctoral Dissertations Graduate School 12-2008 The Microdosimetry of Boron Neutron Capture Therapy Trent L. Nichols University of Tennessee - Knoxville Follow this and additional works at: https://trace.tennessee.edu/utk_graddiss Recommended Citation Nichols, Trent L., "The Microdosimetry of Boron Neutron Capture Therapy. " PhD diss., University of Tennessee, 2008. https://trace.tennessee.edu/utk_graddiss/581 This Dissertation is brought to you for free and open access by the Graduate School at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. To the Graduate Council: I am submitting herewith a dissertation written by Trent L. Nichols entitled "The Microdosimetry of Boron Neutron Capture Therapy." I have examined the final electronic copy of this dissertation for form and content and recommend that it be accepted in partial fulfillment of the requirements for the degree of Doctor of Philosophy, with a major in Physics. Soren P. Sorensen, Major Professor We have read this dissertation and recommend its acceptance: Leo. L Riedinger, Carrol R. Bingham, George W. Kabalka, Laurence F. Miller Accepted for the Council: Carolyn R. Hodges Vice Provost and Dean of the Graduate School (Original signatures are on file with official studentecor r ds.) To the Graduate Council: I am submitting herewith a dissertation written by Trent Lee Nichols entitled “The Microdosimetry of Boron Neutron Capture Therapy.” I have examined the final electronic copy of this dissertation for form and content and recommend that it be accepted in partial fulfillment of the requirements for the degree of Doctor of Philosophy, with a major in Physics. Soren P. Sorensen, Major Professor We have read this dissertation and recommend its acceptance: Leo. L Riedinger Carrol R. Bingham George W. Kabalka Laurence F. Miller Accepted for the Council: Carolyn R Hodges Vice Provost and Dean of the Graduate School (Original signatures are on file with official student records.) The Microdosimetry of Boron Neutron Capture Therapy A Dissertation Presented for the Doctor of Philosophy Degree The University of Tennessee Trent Lee Nichols, MD December 2008 Copyright ©, Trent Lee Nichols, M.D, Ph.D. 2008 All rights reserved ii Dedication This dissertation is dedicated to the memory of my father, Ted Nichols, whose love, support, and guidance has been so important to me. There is not a day that I do not think of him. iii Acknowledgements Earning a Ph.D. is a reflection of all the professors who have influenced and shaped one’s career. It is not possible to thank everyone who has helped me to achieve this milestone. To all who have helped in one way or another, I wish to express my gratitude but there are several however who deserve special recognition. In undergraduate and graduate school, I was fortunate to have many excellent professors. Dr. P. G. Huray, my first physics professor and major professor for my masters degree, sparked my love for physics. Dr. W. E. Deeds taught me to question everything. Drs. R. D. Present, J.R. Thompson, T. A. Callcott, and E. G. Harris taught me how to think as a physicist. Dr. R. W. Lide provided imortant perspectives on life. A special thanks to Dr. M. W. Guidry who taught me how to integrate knowledge from one area of physics and apply it in another. Dr. Guidry’s belief in my abilities has much to do with me having the confidence to pursue this degree over such a long time. He gave me the opportunity of a lifetime by helping me to go to the Niels Bohr Institutet at the Københavns Universitet in København, Denmark. In working on the problem of Boron Neutron Capture Therapy, I have met, talked, and collaborated with colleagues throughout the world. To each I owe gratitude since each has contributed to my understanding of BNCT. In particular, I would like to recognize Drs. R. G. Zamenhof, P. M. Busse, J. Capala, J. C. Yanch, D. Nigg, A. Soloway, R. Barth, G. Smith, and T. Byrnes. In particular, I wish to thank my committee: Drs. S. P. Sorensen, C. R. Bingham, G. W. Kabalka, L. F. Miller, and L. L. Riedinger for being available to help me to obtain a life long goal. Dr. Bingham has been encouraging throughout my career. His quiet optimism has been an important role model. He is always willing to stop to answer questions or provide a new insight into nuclear physics. Early in my career, Dr. Bingham taught me much about experimental nuclear physics. Without the support and encouragement of Dr. Riedinger, I would not have been able to accomplish my goal of a Ph.D. in physics. He taught me electricity and magnetism, brought me into nuclear physics research, and has believed in me. Very iv importantly, he convinced the graduate school to allow me to complete my interupted degree. Dr. Riedinger is a mentor and friend who exemplifies what it means to be a professor of physics. A special thanks to Dr. Miller whose help with the details of neutron beams and the details of the dose calculations was invaluable. He kept me focused on the tasks at hand rather than pursue interesting but unimportant avenues. His thoughts and views on the subject was an important part of this research. Without his cheerful and positive encouragement, this dissertation may have never come to fruition. An excellent mentor is essential to a graduate student. I was fortunate to have Dr. G. Kabalka as my mentor. He has taught me much about being a professional in research and in doing so he has become a close friend and confidant. We have shared research successes together as well as a few disappointments. His optimism, insights, and wisdom has been a positive influence in my life. I am a better person for having had the privilege to work with Dr. Kabalka. The culmination of a Ph.D. requires a major professor who can be critical, helpful, and encouraging all at the same time. Dr. Sorensen has provided me that guidance. He stepped in at a critical point in my research and has guided me to the completion of my degree. He has helped me to regain the critical thinking crucial to being a physicist that years of medical practice has dulled. Without his help and support, I would have likely never completed my degree. Obtaining my Ph.D. has required much sacrifice, understanding, and patience from my family. My parents, Ted and Audrey Nichols, have been supportive throughout my career. My wonderful children, Ted and Frances have long since learned that dad watches television only with a computer multi-tasking some sort of physics related project. I am so very proud of them both and I am enjoying watching their lives unfold. Most importantly of all, I wish to thank my wonderful wife Sally. Without her devotion, patience, support, and love my degree could never have been achieved. She has picked me up when I was down and has carried me through the hard times. She has helped me in every aspect of my dissertation but most importantly she encouraged me v when I was ready to quit. We have shared many good times over the past 30 years and a few bad times. Sally is the love of my life and to her I owe the most. vi Abstract Boron neutron capture therapy (BNCT) is a brachyradiotherapy that exploits the large thermal neutron (~0.025eV) cross-section of 10 B. After absorbing a neutron, a 11 B compound nucleus will spontaneously fission into an alpha particle and a lithium nucleus. An average energy of 2.31 MeV is deposited in a volume on the order of one cell diameter. The large masses and high energies of ion products constitute a high linear energy transfer (LET) reaction. High LET reactions cause double stranded deoxyribonucleic acid (ds-DNA) breaks that lead to cell death because the breaks cannot be accurately repaired. BNCT has been used in clinical trials to treat the aggressive infiltrative brain malignancy, glioblastoma multiforme, and the skin cancer, melanoma. The few studies on melanoma seem to be more promising than the trials on glioblastoma. The cellular level energy deposition pattern, the microdosimetry, reveals the reason for the observed differences. Programs were written modeling cells as ellipsoids arranged in a body centered cubic with nuclei that can be spheres or ellipsoids independent of the cell and non- concentric. The dose was calculated for various boron concentrations in the interstitium, the cell cytoplasm, and the cell nuclei for different geometries. The results demonstrate that cells closely packed receive a larger dose than widely separate cells. Also, the dose increases linearly with boron concentration so that better boron delivery agents will improve the efficacy. Infiltrative glioblastoma cells that are in small clumps or isolated receive a smaller dose than melanoma cells that are tightly packed. The microdosimetric model corresponds to clinically observed results. Also, the model predicts that improved boron delivery agents could make glioblastoma a disease that is curable by BNCT. vii Preface Cancer causes much human suffering as well as economic losses due to lost wages and the cost of therapy. Despite monumental medical efforts, cancer remains difficult to cure for many cell types. Often, treatment regimens cause considerable morbidity and occasional mortality. The treatment regimen often has connected morbidities that are significant enough to cause the patient to miss work for some time after the completion of the therapy. The search continues to find a safe, focused, efficacious radiotherapy with minimal morbidity.