Woodruff School of Mechanical Engineering
NRE 8011/8012 and MP 6011/6012 Seminar
Nuclear & Radiological Engineering and Medical Physics Programs
Clinical and Biological Relevance of a DNA Dosimeter
Dr. Kristen McConnell
University of California San Diego
Thursday, February 21, 2019 at 11:00:00 AM
Boggs Building, Room 3-47
Various radiation types are presently used in radiation therapy: photons, electrons, heavy-charged particles, and neutrons. The fundamental quantity to describe the amount of delivered radiation is dose. Radiation therapy beams are calibrated and monitored using a variety of dosimeters to ensure that the correct physical dose has been administered. However, it has been demonstrated that dose alone is insufficient to describe or predict biological effect, in particular when heavy charged particles or neutrons are used. This dependency on radiation type is governed by differences in energy deposition patterns on a microscopic scale. We have a created solution that branches physics with biology by using deoxyribonucleic acid double-strand breaks as the mechanism for dose detection while accounting for ionization density on the cellular and subcellular/DNA scales. Our dosimeter uses four kilobase pair deoxyribonucleic acid double-strands labeled on one end with fluorescein amidite and on the other with biotin, which is attached to a magnetic streptavidin bead. In the case of a double-strand-break, the strands will be broken into two pieces: the bead/biotin end (unbroken strands + non-fluorescing broken strands) and the fluorescein amidite end (fluorescing broken ends). After irradiation, a magnet is used to physically separate the broken deoxyribonucleic acid pieces from the nonbroken deoxyribonucleic acid strands. A fluorescence reader is used to measure the fluorescence for both broken and unbroken strands and calculate the probability of double-strand breaks (PDSB) using the following formula: PDSB . As preliminary work to establish a benchmark, the dosimeter response was characterized as a function of delivered dose and compared to a Southern Blot analysis to verify that deoxyribonucleic acid double-strand-breaks were the mechanism being measured. After verification, the ability of this dosimeter to detect changes in RBE in low energy x-rays and neutrons was tested against a high energy (6MV) benchmark. Future experiments using the dosimeter will be used to test its ability to detect spatial changes in RBE for protons along the spread out Bragg peak in an attempt to better capitalize on the benefits protons offer for radiotherapy treatment.
Kristen McConnell is currently a medical physics therapy resident at UC San Diego. She began the journey at UT Austin as a mechanical engineering student, and after graduation, she worked as an IT consultant at Accenture, LLP where she participated in various projects for aerospace/defense as well as energy clients. During this time, she also worked on a master's of nuclear engineering at UT Austin. Her time at Accenture highlighted how to make systems perform better while nuclear engineering offered up the benefits for radiation. Medical physics was the overlap of these two worlds, and she finished her Ph.D. in medical physics at UT Health San Antonio in 2018. Her research focuses on the detection of radiation using biological mechanisms to aid in the eventual biological optimization of treatment plans.
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