Real-Time Observation of Radiation-Induced DNA Damage for Radiopharmaceuticals 📝

Author: Denis Bergeron, Brittany Broder, Sean Jollota, Ahtesham Ullah Khan, Michael Lamontagne, Joseph W. Robertson 👨‍🔬

Affiliation: Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin - Madison, Biophysics and Biomedical Research Group, Microsystems and Nanotechnology Division, National Institute of Standards and Technology, National Institute of Standards and Technology 🌍

Abstract:

Purpose: We present new methodology for real-time measurement of radiation-induced DNA damage caused by radiopharmaceuticals. Building on previous efforts to measure DNA fragmentation with nanopore sensors, we are applying this tool to measure in situ DNA scission reactions in the presence of radioisotopes used in radiotherapy.

Methods: A solution of 90Y in 0.04 mol/L HCl was received and diluted gravimetrically to prepare sources for calibration and for addition to DNA-containing reservoirs. Three liquid scintillation sources (1 kBq to 2 kBq at the measurement time) were prepared for counting by the triple-to-double coincidence ratio (TDCR) method with massic activity uncertainty <0.7.%.

Results: Our results demonstrate that supercoiled DNA can serve as an in situ radiation dosimeter for resistive pulse biodosimetry. By using supercoiled DNA we have shown that resistive pulse sensors can be used to assess both single-strand scission reactions as well as double-strand scission reactions. Additionally, by using radionuclides rather than external beams as the radiation source, we demonstrated that single-molecule dosimetry can be performed in real-time.

Conclusion: DNA damage can be assessed by resistive pulse sensors in a manner that is fully compatible with in situ radiotherapeutic isotopes. These tools will enable precision studies of radiopharmaceuticals by providing calibrated real-time dose-damage assessments at the molecular level.

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