Date of Award
Doctor of Philosophy
Soren P. Sorensen
Leo. L Riedinger, Carrol R. Bingham, George W. Kabalka, Laurence F. Miller
Boron neutron capture therapy (BNCT) is a brachyradiotherapy that exploits the large thermal neutron (~0.025eV) cross-section of 10B. After absorbing a neutron, a 11B 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 nonconcentric. 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.
Nichols, Trent L., "The Microdosimetry of Boron Neutron Capture Therapy. " PhD diss., University of Tennessee, 2008.