Evaluating the radioprotective effect of Cimetidine, IMOD, and hybrid radioprotectors agents: An in-vitro study.

INTRODUCTION: There are various radioprotective agents with different mechanisms that help to decrease ionizing radiation side effects. The radioprotective effect of Cimetidine and IMOD was assessed individually and compared with the hybrid radioprotectors agents (HRPAs-IMOD and Cimetidine) on human lymphocyte cells. METHODS: Twenty healthy volunteers (ten men and ten women) participated in the present study. About 75 mL peripheral blood lymphocytes from each individual were collected, and they were divided into 36 groups. Briefly, the blood samples were treated with different concentrations of Cimetidine (12.6 and 25.2 µg/mL) and IMOD (0.04, 0.08, and 0.12 mg/mL), and also a combination of these agents, namely hybrid radioprotectors agents (HRPAs). Besides, the irradiated groups were exposed to 2 and 4 Gy of Co-60 gamma irradiation. The amount of cellular damage was assessed using the micronucleus assay. The repeated measurements and paired T-test statistical analysis were used to compare the micronucleus frequencies in different groups. RESULTS: The micronucleus frequencies were significantly reduced (p < 0.05) in irradiated groups when the non-toxic concentrations of Cimetidine, IMOD, and HRPAs have been used. The reduction in micronucleus frequency was obtained 5-29% for Cimetidine and 40-51% for IMOD in peripheral blood lymphocytes irradiated with 2 Gy. This reduction in 4 Gy irradiation was 8-17% for Cimetidine and 27-37% for IMOD. The HRPAs resulted in a higher radioprotective effect, in a way that they cause up to 58% and 43% micronucleus frequency reduction in 2 and 4 Gy, respectively. CONCLUSION: In conclusion, the HRPAs showed the highest level of radioprotective. In addition, IMOD was remarkably higher radioprotective than Cimetidine, which may be related to its greater non-toxic concentrations.

Accuracy evaluation of distance inverse square law in determining virtual electron source location in Siemens Primus linac.

AIM: The aim of this study is to evaluate the accuracy of the inverse square law (ISL) method for determining location of virtual electron source (SVir) in Siemens Primus linac. BACKGROUND: So far, different experimental methods have presented for determining virtual and effective electron source location such as Full Width at Half Maximum (FWHM), Multiple Coulomb Scattering (MCS), and Multi Pinhole Camera (MPC) and Inverse Square Law (ISL) methods. Among these methods, Inverse Square Law is the most common used method. MATERIALS AND METHODS: Firstly, Siemens Primus linac was simulated using MCNPX Monte Carlo code. Then, by using dose profiles obtained from the Monte Carlo simulations, the location of SVir was calculated for 5, 7, 8, 10, 12 and 14 MeV electron energies and 10 cm × 10 cm, 15 cm × 15 cm, 20 cm × 20 cm and 25 cm × 25 cm field sizes. Additionally, the location of SVir was obtained by the ISL method for the mentioned electron energies and field sizes. Finally, the values obtained by the ISL method were compared to the values resulted from Monte Carlo simulation. RESULTS: The findings indicate that the calculated SVir values depend on beam energy and field size. For a specific energy, with increase of field size, the distance of SVir increases for most cases. Furthermore, for a special applicator, with increase of electron energy, the distance of SVir increases for most cases. The variation of SVir values versus change of field size in a certain energy is more than the variation of SVir values versus change of electron energy in a certain field size. CONCLUSION: According to the results, it is concluded that the ISL method can be considered as a good method for calculation of SVir location in higher electron energies (14 MeV).

Artificial neural network based gynaecological image-guided adaptive brachytherapy treatment planning correction of intra-fractional organs at risk dose variation.

PURPOSE: Intra-fractional organs at risk (OARs) deformations can lead to dose variation during image-guided adaptive brachytherapy (IGABT). The aim of this study was to modify the final accepted brachytherapy treatment plan to dosimetrically compensate for these intra-fractional organs-applicators position variations and, at the same time, fulfilling the dosimetric criteria. MATERIAL AND METHODS: Thirty patients with locally advanced cervical cancer, after external beam radiotherapy (EBRT) of 45-50 Gy over five to six weeks with concomitant weekly chemotherapy, and qualified for intracavitary high-dose-rate (HDR) brachytherapy with tandem-ovoid applicators were selected for this study. Second computed tomography scan was done for each patient after finishing brachytherapy treatment with applicators in situ. Artificial neural networks (ANNs) based models were used to predict intra-fractional OARs dose-volume histogram parameters variations and propose a new final plan. RESULTS: A model was developed to estimate the intra-fractional organs dose variations during gynaecological intracavitary brachytherapy. Also, ANNs were used to modify the final brachytherapy treatment plan to compensate dosimetrically for changes in 'organs-applicators', while maintaining target dose at the original level. CONCLUSIONS: There are semi-automatic and fast responding models that can be used in the routine clinical workflow to reduce individually IGABT uncertainties. These models can be more validated by more patients' plans to be able to serve as a clinical tool.

Optimum organ volume ranges for organs at risk dose in cervical cancer intracavitary brachytherapy.

PURPOSE: To analyze the optimum organ filling point for organs at risk (OARs) dose in cervical cancer high-dose-rate (HDR) brachytherapy. MATERIAL AND METHODS: In a retrospective study, 32 locally advanced cervical cancer patients (97 insertions) who were treated with 3D conformal external beam radiation therapy (EBRT) and concurrent chemotherapy during 2010-2013 were included. Rotterdam HDR tandem-ovoid applicators were used and computed tomography (CT) scanning was performed after each insertion. The OARs delineation and GEC-ESTRO-based clinical target volumes (CTVs) contouring was followed by 3D forward planning. Then, dose volume histogram (DVH) parameters of organs were recorded and patients were classified based on their OARs volumes, as well as their inserted tandem length. RESULTS: The absorbed dose to point A ranged between 6.5-7.5 Gy. D0.1cm(3) and D2cm(3) of the bladder significantly increased with the bladder volume enlargement (p value < 0.05). By increasing the bladder volume up to about 140 cm(3), the rectum dose was also increased. For the cases with bladder volumes higher than 140 cm(3), the rectum dose decreased. For bladder volumes lower than 75 cm(3), the sigmoid dose decreased; however, for bladder volumes higher than 75 cm(3), the sigmoid dose increased. The D2cm(3) of the bladder and rectum were higher for longer tandems than for shorter ones, respectively. The divergence of the obtained results for different tandem lengths became wider by the extension of the bladder volume. The rectum and sigmoid volume had a direct impact on increasing their D0.1cm(3) and D2cm(3) , as well as decreasing their D10, D30, and D50. CONCLUSIONS: There is a relationship between the volumes of OARs and their received doses. Selecting a bladder with a volume of about 70 cm(3) or less proved to be better with regards to the dose to the bladder, rectum, and sigmoid.

A comparison of organs at risk doses in GYN intracavitary brachytherapy for different tandem lengths and bladder volumes.

The purpose of this study was to investigate the concurrent effects of tandem length and bladder volume on dose to pelvic organs at risk (OARs) in HDR intracavitary brachytherapy treatment of cervical cancer. Twenty patients with locally advanced cervical cancer were selected for brachytherapy using Rotterdam applicators. The patients were CT scanned twice with empty and full bladder. Two treatment plans were prepared on each of the image sets. Patients were categorized into two groups; those treated with a tandem length of 4 cm or smaller (T ≤ 4 cm) and those with tandem length larger than 4 cm (T > 4 cm). Only one tandem tip angle of 30° was studied. Dose-volume histograms (DVHs) of OARs were calculated and compared. Bladder dose was significantly affected by both bladder volume and tandem physical length for T ≤ 4 cm. This was reflected on the values obtained for D2cm³, D1cm³, and D0.1cm³ for both empty and full bladder cases. When T > 4 cm, no correlation could be established between variations in bladder dose and blad-der volume. Rectum dose was generally lower when the bladder was empty and T > 4 cm. Dose to sigmoid was increased when T > 4 cm; this increase was larger when the bladder was full. Our results suggest that, for tandems longer than 4 cm, keeping the bladder empty may reduce the dose to rectum and sigmoid. This is contrary to cases where a shorter than 4 cm tandem is used in which a full bladder (about 50-120 cm³) tends to result in a lower dose to rectum and sigmoid. Attention should be given to doses to sigmoid with long tandem lengths, as a larger tandem generally results in a larger dose to sigmoid.

Evaluating the utility of "3D Slicer" as a fast and independent tool to assess intrafractional organ dose variations in gynecological brachytherapy.

PURPOSE: To demonstrate the utility of "3D Slicer" for easy treatment verification by comparing dose-volume histograms (DVHs) calculated on pretreatment and posttreatment images. METHODS AND MATERIALS: Thirty cervical cancer patients were CT scanned twice: first for treatment planning and a second time after the dose delivery. The initial plan was manually duplicated on the posttreatment image set in Flexiplan treatment planning system, and DVH parameters were calculated. Pretreatment and posttreatment images, organ structures, and plan data were exported from the treatment planning system to 3D Slicer to validate DVH parameter calculation with 3D Slicer. The gamma analysis was used to compare Flexiplan and 3D Slicer DVHs. Posttreatment images were rigidly fused on the initial CT to automatically transfer the data of the pretreatment plan onto the posttreatment images. DVH parameters were calculated in 3D Slicer for both image sets, and their relative variations were compared. RESULTS: In calculating DVH parameter variations, no significant differences were observed between Flexiplan and 3D Slicer. Where the registration accuracy was better than 0.03, they returned similar results for D2 cm(3) of bladder, rectum, and sigmoid. Mean and standard deviation of DVH parameters were calculated on pretreatment and posttreatment images for several organs; both the manually duplicated plan and the automatically registered plan in SlicerRT returned comparable relative variations of these parameters. For 88% of the organs, more than 95% of the DVH dose bins passed the gamma analysis. CONCLUSIONS: We tested an automated DVH assessment method with an imaging freeware, 3D Slicer, for use in image-guided adaptive brachytherapy. SlicerRT is a viable verification tool to report and detect DVH variations between different contoured images series.

Monte Carlo Determination of Dosimetric Parameters of a New (125)I Brachytherapy Source According to AAPM TG-43 (U1) Protocol.

BACKGROUND: (125)I is one of the important sources frequently used in brachytherapy. Up to now, several different commercial models of this source type have been introduced to the clinical radiation oncology applications. Recently, a new source model, IrSeed-125, has been added to this list. The aim of the present study is to determine the dosimetric parameters of this new source model based on the recommendations of TG-43 (U1) protocol using Monte Carlo simulation. METHODS: The dosimetric characteristics of Ir-125 including dose rate constant, radial dose function, 2D anisotropy function and 1D anisotropy function were determined inside liquid water using MCNPX code and compared to those of other commercially available iodine sources. RESULTS: The dose rate constant of this new source was found to be 0.983+0.015 cGyh-1U-1 that was in good agreement with the TLD measured data (0.965 cGyh-1U-1). The 1D anisotropy function at 3, 5, and 7 cm radial distances were obtained as 0.954, 0.953 and 0.959, respectively. CONCLUISON: The results of this study showed that the dosimetric characteristics of this new brachytherapy source are comparable with those of other commercially available sources. Furthermore, the simulated parameters were in accordance with the previously measured ones. Therefore, the Monte Carlo calculated dosimetric parameters could be employed to obtain the dose distribution around this new brachytherapy source based on TG-43 (U1) protocol.

Production, Quality Control and Pharmacokinetic Studies of (177)Lu-EDTMP for Human Bone Pain Palliation Therapy Trials.

Developing new bone pain palliation agents is a mandate in handling end-stage cancer patients around the world. Possibly, Lu-177 ethylenediaminetetramethylene phosphonic acid ((177)Lu-EDTMP) is a therapeutic agent which can be widely used in bone palliation therapy. In this study, (177)Lu-EDTMP complex was prepared successfully using synthesized EDTMP ligand and (177)LuCl3. Lu-177 chloride was obtained by thermal neutron irradiation (4 × 10(13) n.cm(-2)s(-1)) of natural Lu2O3 samples. Radiochemical purity of (177)Lu-EDTMP was determined by ITLC (more than 99%). Stability studies of the final preparations in the presence of human serum were performed. The biodistribution of (177)Lu-EDTMP and (177)LuCl3 in wild-type rats was studied by SPECT imaging. A comparative accumulation study for (177)Lu-EDTMP and (177)LuCl3 was performed for vital organs up to 7 days. The complex was obtained in high radiochemical purity (more than 99%). The complex was stable in vitro in presence of human serum as well as final formulation. Significant bone uptake (> 70%) was observed for the radiopharmaceutical. Due to better physical properties of Lu-177 compared to Sm-153 and acceptable biodistribution results of the compound, (177)Lu-EDTMP seemed to be an interesting new candidate for clinical trials for bone pain palliation therapy.