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Direct Measurement of a Change in Biological Damage Along a 160 MeV Proton Bragg Curve Using a Novel DNA Dosimeter

K McConnell1*, C Chang1,2, A Giebeler2, L Liu2, L Zhu Qu2, K Moore1, V Moiseenko1, (1) UC San Diego, San Diego, CA, (2) California Protons Cancer Therapy Center, San Diego, CA


(Wednesday, 7/15/2020) 11:30 AM - 12:30 PM [Eastern Time (GMT-4)]

Room: Track 3

Purpose: Incorporating variable relative biological effectiveness models into proton radiotherapy plan optimization with pencil beam scanning has been advocated. Energy deposition patterns at a microscopic scale are known to vary along the proton track with a dramatic increase in ionization density at the Bragg peak (BP). Interrogation at the DNA level paves the way to use mechanistic models to describe biological response on a cellular scale, e.g., cell survival. Using a novel DNA dosimeter that quantifies a basic unit, DNA double-strand breaks (DSB), the probability of DSB (PDSB) was directly measured as a function of dose deposition along a 160 MeV proton Bragg Curve (BC) whose expected BP was at 17.29 cm.

Methods: DNA dosimeters consisting of four kilobase pair double-stranded DNA labeled with biotin/streptavidin beads and fluorescein on opposing ends were created. Ten (10) uL of dosimeter was placed in 1 mm diameter microcapillary tubes and irradiated perpendicular to a 160 MeV 10x10 cm tightly-packed spot pattern. Five dosimeters each at 12 depths were irradiated in water (1 mm sampling around BP). A nominal 30Gy was delivered at each point, and the experiment was repeated with a smaller subset (5 depths) to 60Gy. A machined insert held five dosimeters plus a PTW Advanced Markus chamber for absolute dose verification. The PDSB was divided by the chamber dose reading to obtain PDSB/Gy.

Results: The PDSB/Gy for the 30Gy samples were 0.0030±0.0003 (5.22 cm), 0.0036±0.0001 (10.22 cm), 0.0035±0.0003 (17.12 cm), 0.0063±0.0026 (17.22 cm), 0.0029±0.0002 (17.32 cm), and 0.0027±0.0001 (17.72 cm). For the 60Gy samples, the values were 0.0027±0.0001 (10.22 cm), 0.0027±0.0002 (17.22 cm), 0.0026±0.0002 (17.32 cm), and 0.0024±0.0002 (17.42 cm).

Conclusion: Changes in PDSB along the BC have been observed with the novel DNA dosimeter. PDSB maximized at the BP for 30Gy, while this maximization effect was not pronounced at 60Gy.

Funding Support, Disclosures, and Conflict of Interest: KLM reports income for personal consulting and speakers honoraria from Varian Medical Systems.


Not Applicable / None Entered.


Not Applicable / None Entered.

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