Impact of a 1.5 T magnetic field on DNA damage in MRI-guided HDR brachytherapy

Abstract

Some studies have suggested that the presence of a static magnetic field (SMF) during irradiation alters biological damage. Since MRI-guided radiotherapy is becoming increasingly common, we constructed a DNAbased detector to assess the effect of a 1.5 T SMF on DNA damage during high dose rate (HDR) brachytherapy irradiation. Methods: Block phantoms containing a small cavity for the placement of plasmid DNA (pBR322) samples were 3-D printed with biocompatible tissue equivalent material. The phantom was CT scanned and an HDR brachytherapy treatment plan was designed to deliver 20 Gy and 30 Gy doses to the DNA samples in the presence and absence of a 1.5 T SMF. Relative yields of single-and double-strand breaks (SSBs and DSBs, respectively) were computed from gel electrophoresis images of the DNA band intensities and averaged over sample sizes ranging from 12 to 30. Radiation dose was also measured in the presence and absence of the 1.5 T SMF using GafChromic™ EBT3 film placed in the coronal, sagittal, and axial planes. Results: The average yield of DNA with SSBs and DSBs in the presence and absence of the SMF showed no statistically significant differences (all p ≥ 0.17). Differences in the net optical densities of the EBT3 films for each plane were within experimental uncertainty, suggesting no dose difference in the presence and absence of the SMF. Conclusions: HDR irradiation in the presence of the 1.5 T SMF did not alter dose deposition to the DNA cavity nor change SSB and DSB DNA damage.

Technical note: Characterization and practical applications of a novel plastic scintillator for online dosimetry for an ultrahigh dose rate (FLASH)

“…The first experiment consisted of the irradiation of plasmid DNA-based detectors previously described in the literature. 39,40 The detectors consist of ∼1 × 1 × 1-mm 3 vials of plasmid DNA embedded in a 30 × 30 × 5-mm 3 acrylic cassette, with the detectors located at the superior surface (e.g., exit window) of the acrylic cassette. The exit window is chosen as the dosimetric point of interest as closest physically to the plasmid DNA detectors.…”

“…The plastic scintillator was used in tandem with a Gafchromic EBT-XD film to measure the transmission dose in two FLASH-RT experiments-plasmid DNA detectors, 39,41 and cell plates that consisted either of Zebrafish embryos in well-type cell plates or conventional cell cultures in petri dishes. The results are shown in Figure 6.…”

Quantifying the DNA-damaging Effects of FLASH Irradiation With Plasmid DNA

“…To this end, pBR322 plasmid DNA (Thermo Fisher Scientific, Inc.) was selected for its lack of higher-level biological processes that might otherwise confound the 𝑅𝐵𝐸 𝐷𝑆𝐵 of FDR versus SDR irradiation. This reductionist DNA approach has been used in other radiotherapy DNA damage studies, [30][31][32][33] and lends itself naturally to study whether differences observed between FDR and SDR irradiation can be understood at least partially in terms of fundamental radiochemical mechanisms or whether they are attributed solely to higher level biochemical cellular pathways and/or biological system responses. To test this, we constructed DNA-based phantoms comprising plasmid DNA and exposed them to FDR and SDR irradiation to quantify the resulting yields of SSBs and DSBs.…”