Monte Carlo Study of Radiation Dose Enhancement by Gadolinium in Megavoltage and High Dose Rate Radiotherapy

Abstract

MRI is often used in tumor localization for radiotherapy treatment planning, with gadolinium (Gd)-containing materials often introduced as a contrast agent. Motexafin gadolinium is a novel radiosensitizer currently being studied in clinical trials. The nanoparticle technologies can target tumors with high concentration of high-Z materials. This Monte Carlo study is the first detailed quantitative investigation of high-Z material Gd-induced dose enhancement in megavoltage external beam photon therapy. BEAMnrc, a radiotherapy Monte Carlo simulation package, was used to calculate dose enhancement as a function of Gd concentration. Published phase space files for the TrueBeam flattening filter free (FFF) and conventional flattened 6MV photon beams were used. High dose rate (HDR) brachytherapy with Ir-192 source was also investigated as a reference. The energy spectra difference caused a dose enhancement difference between the two beams. Since the Ir-192 photons have lower energy yet, the photoelectric effect in the presence of Gd leads to even higher dose enhancement in HDR. At depth of 1.8 cm, the percent mean dose enhancement for the FFF beam was 0.38±0.12, 1.39±0.21, 2.51±0.34, 3.59±0.26, and 4.59±0.34 for Gd concentrations of 1, 5, 10, 15, and 20 mg/mL, respectively. The corresponding values for the flattened beam were 0.09±0.14, 0.50±0.28, 1.19±0.29, 1.68±0.39, and 2.34±0.24. For Ir-192 with direct contact, the enhanced were 0.50±0.14, 2.79±0.17, 5.49±0.12, 8.19±0.14, and 10.80±0.13. Gd-containing materials used in MRI as contrast agents can also potentially serve as radiosensitizers in radiotherapy. This study demonstrates that Gd can be used to enhance radiation dose in target volumes not only in HDR brachytherapy, but also in 6 MV FFF external beam radiotherapy, but higher than the currently used clinical concentration (>5 mg/mL) would be needed.

Monte Carlo simulations guided by imaging to predict the in vitro ranking of radiosensitizing nanoparticles

“…30,31 It is likely a consequence of the fact that the dose was averaged over the whole cell structure whose volume is much larger than that of the clusters (eg, the cell structure's volume is 904.8 µm 3 while the sum of the iron …”

“…Then, cells were rinsed again and dehydrated through a graded series of ethanol concentrations (30,50,70,80,90, and 100% for 5 min each) and embedded in epoxy-based resin (Embed 812, DDSA, NMA, and DMP30; Electron Microscopy Sciences, France). After resin polymerization and plastic dissolution with xylene, samples were cut in 90 nm thick slices using Ultra-cut E ultramicrotome (Reichert-Yung).…”

“…These simulations have been extensively detailed in the literature. 8,29,30 In this counterexample, we have decided to fix the number of clusters (=10), the number of NPs per cluster (=100) and radius of each cluster (=250 nm), which are the same for our 3 NPs.…”

Superficial and peripheral dose in compensator‐based FFF beam IMRT

“…Published phase space files for 6 MV FFF and flattened beams, generated using the actual geometry of the TrueBeam accelerator (Varian Medical System, Palo Alto, CA, USA) above the collimator moving jaws,16 were used as the input radiation source to BEAMnrc. Those phase space files were validated with measurements17 and successfully used in previous studies 9, 18, 19. Water phantom was simulated using DOSXYZnrc for dose distribution calculations 20…”

Prostate cancer radiotherapy: potential applications of metal nanoparticles for imaging and therapy

“…16,60 These experimental studies demonstrating Gd as a radiation sensitizer are further supported by a recent Monte Carlo simulation study. Zhang et al 65 calculated DEFs as a function of Gd concentration for 6-MV photons with and without the use of a flattening filter and for HDR BT with an iridium-192 source. The study predicted concentration-dependent dose enhancement for Gd-containing materials in HDR BT and 6-MV flattening filter-free EBRT at concentrations .5 mg ml 21 , higher than those currently used in the clinic.…”