Behnaz Behmand

@article{nokey,

title = {Microdosimetry calculations in situ for clinically relevant photon sources and their correlation with the early DNA damage response},

author = {Mirta Dumančić and Jonathan Kalinowski and Victor D Diaz-Martinez and Joanna Li and Behnaz Behmand and Joseph M DeCunha and Shirin A Enger},

url = {https://aapm.onlinelibrary.wiley.com/doi/10.1002/mp.17979},

doi = {10.1002/mp.17979},

issn = {2473-4209},

year  = {2025},

date = {2025-07-15},

urldate = {2025-07-15},

journal = {Medical Physics},

volume = {52},

number = {e17979},

issue = {7},

abstract = {Background:

Radiobiological data suggests variations in relative biological effectiveness (RBE) between clinically used photon-based sources. A microdosimetric formalism using Monte Carlo (MC) methods can mechanistically describe the photon RBE. Experimentally derived RBE based on DNA double-strand breaks (RBEDSB) has been shown to scale with the microdosimetry quantity dose-mean lineal energy (yD).



Purpose:

To calculate microdosimetric spectra for clinically relevant photon sources, spanning from soft x-rays produced by a 50 kVp x-ray source through various brachytherapy sources up to a 6 MV medical linac. Furthermore, we investigated the correlation between RBEDSB and yD of different photon sources.



Methods:

Photon sources simulated include low-energy x-rays (50 kVp), orthovoltage x-rays (225 kVp), high-dose-rate brachytherapy sources (75Se, 192Ir and 60Co), and a 6 MV medical linac. Secondary electron spectra at the cellular level were calculated for in vitro cell irradiation setups using Geant4 MC-based packages, RapidBrachyMCTPS and RapidExternalBeam. The obtained spectra were used in MicroDose, a microdosimetry simulation software, to obtain microdosimetric quantities, including single-event lineal energy (y) and specific energy (z) spectra, and dose-mean and frequency-mean quantities (yF, yD, zsF, zsD). Uniform spherical targets (1–14 μm radius) and realistic HeLa and PC3 cell nucleus models were simulated using cell size data obtained from literature and nuclei size data from confocal microscopy imaging. Radiobiological experiments using γH2AX foci quantified DNA double-strand breaks for HeLa and PC3 cells after irradiations with 50 and 225 kVp, 192Ir, and 6 MV linac, and RBEDSB was determined using 225 kVp as the reference.



Results:

The calculated yD (yF) is within the 3.5–1.2 keV/μm range (1.8–0.2 keV/μm) for 1 μm simulated target size between the lowest energy 50 kVp x-ray source and the highest energy 6 MV linac source, respectively. For the HeLa and PC3 cell nuclei models based on microscopy data, yD (yF) spans from 1.6 to 0.6 keV/μm (0.7 to 0.2 keV/μm). When compared between different target sizes, yD (yF) ranges from 3.5 to 1.0 (1.8–0.4) keV/μm between 1 and 10 μm radius targets for the 50 kVp x-ray source. A smaller change is observed for 6 MV linac, ranging from 1.2 to 0.5 keV/μm and 0.23 to 0.22 keV/μm for yD and yF, respectively. For the simulated 75Se source currently under investigation, the calculated yD values are 11%–24% higher relative to those of 192Ir in the range of target sizes between 1 and 14 μm in radius. RBEDSB for HeLa cells was 1.4 ± 0.7 for 50 kVp x-rays, 0.5 ± 0.2 for 192Ir, and 0.7 ± 0.4 for 6 MV linac irradiations. For PC3 cells, RBEDSB was 1.3 ± 0.6, 0.8 ± 0.4 and 0.5 ± 0.3 for 50 kVp, 192Ir and 6 MV linac, respectively. Measured RBEDSB values are consistent with yD ratios of the corresponding photon sources for HeLa and PC3 nucleus models.



Conclusions:

Microdosimetric spectra strongly depend on the simulated energy of photon sources and target size, with yD and zsD decreasing by a factor of ≈2–3 between diagnostic 50 kVp and 6 MV therapeutic x-rays for target sizes from 1–14 μm in radius. The early damage RBEDSB indicates this stochastic change in energy density between various photon sources as the yields of γH2AX foci per nucleus scale with yD of the source.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cyr2024-me,

title = {Establishing a standardized murine orthotopic intra-rectal model for the study of colorectal adenocarcinoma},

author = {Mélodie Cyr and Naim Chabaytah and Joud Babik and Behnaz Behmand and Guillaume St-Jean and Shirin A. Enger},

url = {https://jgo.amegroups.org/article/view/93989},

doi = {10.21037/jgo-24-515},

isbn = {2078-6891},

year  = {2024},

date = {2024-12-31},

urldate = {2024-12-31},

journal = {Journal of Gastrointestinal Oncology},

volume = {15},

issue = {6},

pages = {2578-2587},

abstract = {Background: Orthotopic models offer a more accurate representation of colorectal cancer (CRC) compared to subcutaneous models. Despite promising results from the reported intra-rectal models, establishing a standardized method for CRC research remains challenging due to model variability, hindering comprehensive studies on CRC pathogenesis and treatment modalities, such as brachytherapy. This study aimed to establish a standardized workflow for an orthotopic intra-rectal animal model to induce the growth of colorectal adenocarcinoma in male and female mice.



Methods: HT-29 colorectal adenocarcinoma cells were injected into the rectal mucosa of female (n=21) and male (n=26) non-obese diabetic severe combined immunodeficiency (NOD SCID) gamma (NSG) mice. Mice were placed on a 45° wedge elevating their pelvis for better visualization of the anus. Tumor growth and localization were monitored using a 7-T magnetic resonance imaging (MRI) scanner with rapid acquisition with relaxation echo (RARE) sequence at weeks 1, 2, and 3 post-cell instillation. Once tumors reached 5-8 mm in diameter, the mice were euthanized. Histopathology and immunohistochemical analyses confirmed the tumors' morphology, including necrosis, vascularity (CD-31) and apoptosis (cleaved caspase-3).



Results: There was a 92% and 95% tumor growth success rate in male and female mice, respectively. Tumors grew to 5-8 mm in diameter within ~20 days. No significant difference in tumor size was observed between genders. Tumor morphology was consistent across cases. Most tumors exhibited a lack of central blood vessels, accompanied by varying degrees of necrosis and apoptosis, whereas external portions were highly vascularized.



Conclusions: An orthotopic intra-rectal model was successfully developed. This model will be used in future studies to evaluate the efficacy of CRC treatments.



Keywords: Colorectal adenocarcinoma; HT-29; animal model; orthotopic intra-rectal.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Relative biological effectiveness of clinically relevant photon energies for the survival of human colorectal, cervical, and prostate cancer cell lines},

author = {Joanna Li and Naim Chabaytah and Joud Babik and Behnaz Behmand and Hamed Bekerat and Tanner Connell and Michael D C Evans and Russell Ruo and Te Vuong and Shirin A Enger 6},

doi = {10.1088/1361-6560/ad7d5a},

year  = {2024},

date = {2024-09-19},

journal = {Physics in Medicine and Biology },

keywords = {},

pubstate = {published},

tppubtype = {article}

}