Radiosensitization effect of radiofrequency hyperthermia in the presence of PEGylated-gold nanoparticles on the MCF-7 breast cancer cells under 6 MeV electron irradiation.

Purpose: The purpose of the study was to investigate the radiosensitization effect of radiofrequency (RF) hyperthermia in combination with PEGylated gold nanoparticles (PEG-GNPs) on MCF-7 breast cancer cells under electron beam radiotherapy (EBRT) based on the clonogenic assay. Materials and Methods: The cell death of MCF-7 breast cancer cells treated with 13.56 MHz capacitive RF hyperthermia (power: 150W) for 2, 5, 10, and 15 min combined with 6 MeV EBRT, with a dose of 2 Gy, was evaluated in the presence of 20 nm PEG-GNPs with a low nontoxic concentration (20 mg/l). All the treatment groups were incubated for 14 days. Thereafter, survival fractions and viability of the cells were calculated and analyzed against the control group. Results: The presence of PEG-GNPs inside the MCF-7 cancer cells during electron irradiation decreased cell survival significantly (16.7%) compared to irradiated cells without GNPs. Applying hyperthermia before electron irradiation with a capacitive RF system decreased cell survival by about 53.7%, while hyperthermia without irradiation did not show any significant effect on cell survival. Combining the hyperthermia with the presence of PEG-GNPs in the cells decreased the cell survival by about 67% at the electron irradiation, showing their additive radiosensitization effect. Conclusion: Low nontoxic concentration of 20 nm PEG-GNPs increases the radiosensitization effect of combining 6 MeV EBRT and RF hyperthermia on MCF-7 cancer cells. Combining hyperthermia with PEG-GNPs in electron radiotherapy could be an appropriate method for enhancing radiotherapy effectiveness on cancerous cells which can be studied on different cells and electron energies in future research.

Effect of 13.56 MHz radiofrequency hyperthermia on mitotic cell cycle arrest in MCF7 breast cancer cell line and suggest a time interval for radiotherapy.

Introduction: After surgery, radiotherapy is the most common technique to treat breast cancer. Over the past decades, the thermal effects of radiofrequency-wave hyperthermia combined with radiotherapy have been used to increase radiosensitivity in cancer treatment. The cells have various radiation and thermal sensitivities at different stages of the mitotic cycle. Furthermore, ionizing radiation and the thermal effect of hyperthermia affect the cells' mitotic cycle and can partly induce cell cycle arrest. However, the time interval between hyperthermia and radiotherapy, as an essential factor influencing hyperthermia effect on cancer cells' cycle arrest, has not been studied before. In this study, we investigated the effect of hyperthermia on the MCF7 cancer cell cycle arrest in mitotic cycles at various selected time intervals after hyperthermia to find and propose appropriate time intervals between hyperthermia and radiotherapy. Method and Materials: In this experimental study, we used the MCF7 breast cancer cell line to investigate the effect of 13.56 MHz hyperthermia (at a temperature of 43°C for a period of 20 min) on their cell cycle arrest. We performed the flowcytometry assay to assess the changes in the mitotic phases of the cell population at different time intervals (1, 6, 24, and 48 h) after hyperthermia. Results: Our flowcytometry results indicated the 24-h time interval has the most significant effect on the cell population at S and G2/M phases. Therefore, the 24-h time interval can be proposed as the most appropriate time after hyperthermia for carrying out combinational radiotherapy procedure. Conclusion: Among various investigated time intervals examined in our research, the 24-h time interval can be proposed as the most appropriate time between hyperthermia and radiotherapy for combinational therapy of breast cancer cells.

Introducing new plan evaluation indices for prostate dose painting IMRT plans based on apparent diffusion coefficient images.

BACKGROUND: Dose painting planning would be more complicated due to different levels of prescribed doses and more complex evaluation with conventional plan quality indices considering uniform dose prescription. Therefore, we tried to introduce new indices for evaluating the dose distribution conformity and homogeneity of treatment volumes based on the tumoral cell density and relative volumes of each lesion in prostate IMRT. METHODS: CT and MRI scans of 20 male patients having local prostate cancer were used for IMRT DP planning. Apparent diffusion coefficient (ADC) images were imported to a MATLAB program to identify lesion regions based on ADC values automatically. Regions with ADC values lower than 750 mm2/s and regions with ADC values higher than 750 and less than 1500 mm2/s were considered CTV70Gy (clinical tumor volume with 70 Gy prescribed dose), and CTV60Gy, respectively. Other regions of the prostate were considered as CTV53Gy. New plan evaluation indices based on evaluating the homogeneity (IOE(H)), and conformity (IOE(C)) were introduced, considering the relative volume of each lesion and cellular density obtained from ADC images. These indices were compared with conventional homogeneity and conformity indices and IOEs without considering cellular density. Furthermore, tumor control probability (TCP) was calculated for each patient, and the relationship of the assessed indices were evaluated with TCP values. RESULTS: IOE (H) and IOE (C) with considering cellular density had significantly lower values compared to conventional indices and IOEs without considering cellular density. (P < 0.05). TCP values had a stronger relationship with IOE(H) considering cell density (R2 = -0.415), and IOE(C) without considering cell density (R2 = 0.624). CONCLUSION: IOE plan evaluation indices proposed in this study can be used for evaluating prostate IMRT dose painting plans. We suggested to consider cell densities in the IOE(H) calculation formula and it's appropriate to calculate IOE(C) without considering cell density values.

Estimating cancer risks due to whole lungs low dose radiotherapy with different techniques for treating COVID-19 pneumonia.

BACKGROUND: Low dose radiotherapy (LDRT) of whole lungs with photon beams is a novel method for treating COVID-19 pneumonia. This study aimed to estimate cancer risks induced by lung LDRT for different radiotherapy delivery techniques. METHOD: Four different radiotherapy techniques, including 3D-conformal with anterior and posterior fields (3D-CRT AP-PA), 3D-conformal with 8 coplanar fields (3D-CRT 8 fields), eight fields intensity-modulated radiotherapy (IMRT), and volumetric modulated arc therapy using 2 full arcs (VMAT) were planned on the CT images of 32 COVID-19 patients with the prescribed dose of 1 Gy to the lungs. Organ average and maximum doses, and PTV dose distribution indexes were compared between different techniques. The radiation-induced cancer incidence and cancer-specific mortality, and cardiac heart disease risks were estimated for the assessed techniques. RESULTS: In IMRT and VMAT techniques, heart (mean and max), breast (mean, and max), and stomach (mean) doses and also maximum dose in the body were significantly lower than the 3D-CRT techniques. The calculated conformity indexes were similar in all the techniques. However, the homogeneity indexes were lower (i.e., better) in intensity-modulated techniques (P < 0.03) with no significant differences between IMRT and VMAT plans. Lung cancer incident risks for all the delivery techniques were similar (P > 0.4). Cancer incidence and mortality risks for organs located closer to lungs like breast and stomach were higher in 3D-CRT techniques than IMRT or VMAT techniques (excess solid tumor cancer incidence risks for a 30 years man: 1.94 ± 0.22% Vs. 1.68 ± 0.17%; and women: 6.66 ± 0.81% Vs. 4.60 ± 0.43%: cancer mortality risks for 30 years men: 1.63 ± 0.19% Vs. 1.45 ± 0.15%; and women: 3.63 ± 0.44% Vs. 2.94 ± 0.23%). CONCLUSION: All the radiotherapy techniques had low cancer risks. However, the overall estimated risks induced by IMRT and VMAT radiotherapy techniques were lower than the 3D-CRT techniques and can be used clinically in younger patients or patients having greater concerns about radiation induced cancers.

The feasibility of a dose painting procedure to treat prostate cancer based on mpMR images and hierarchical clustering.

BACKGROUND: We aimed to assess the feasibility of a dose painting (DP) procedure, known as simultaneous integrated boost intensity modulated radiation Therapy (SIB-IMRT), for treating prostate cancer with dominant intraprostatic lesions (DILs) based on multi-parametric magnetic resonance (mpMR) images and hierarchical clustering with a machine learning technique. METHODS: The mpMR images of 120 patients were used to create hierarchical clustering and draw a dendrogram. Three clusters were selected for performing agglomerative clustering. Then, the DIL acquired from the mpMR images of 20 patients were categorized into three groups to have them treated with a DP procedure being composed of three planning target volumes (PTVs) determined as PTV1, PTV2, and PTV3 in treatment plans. The DP procedure was carried out on the patients wherein a total dose of 80, 85 and 91 Gy were delivered to the PTV1, PTV2, and PTV3, respectively. Dosimetric and radiobiologic parameters [Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP)] of the DP procedure were compared with those of the conventional IMRT and Three-Dimensional Conformal Radiation Therapy (3DCRT) procedures carried out on another group of 20 patients. A post-treatment follow-up was also made four months after the radiotherapy procedures. RESULTS: All the dosimetric variables and the NTCPs of the organs at risks (OARs) revealed no significant difference between the DP and IMRT procedures. Regarding the TCP of three investigated PTVs, significant differences were observed between the DP versus IMRT and also DP versus 3DCRT procedures. At post-treatment follow-up, the DIL volumes and apparent diffusion coefficient (ADC) values in the DP group differed significantly (p-value < 0.001) from those of the IMRT. However, the whole prostate ADC and prostate-specific antigen (PSA) indicated no significant difference (p-value > 0.05) between the DP versus IMRT. CONCLUSIONS: The results of this comprehensive clinical trial illustrated the feasibility of our DP procedure for treating prostate cancer based on mpMR images validated with acquired patients' dosimetric and radiobiologic assessment and their follow-ups. This study confirms significant potential of the proposed DP procedure as a promising treatment planning to achieve effective dose escalation and treatment for prostate cancer. TRIAL REGISTRATION: IRCT20181006041257N1; Iranian Registry of Clinical Trials, Registered: 23 October 2019, https://en.irct.ir/trial/34305 .

Radiosensitization of breast cancer cells using AS1411 aptamer-conjugated gold nanoparticles.

BACKGROUND: Gold nanoparticles (GNPs) have been used to sensitize cancer cells and enhance the absorbed dose delivered to such cells. Active targeting can provide specific effect and higher uptake of the GNPs in the tumor cells, while having small effect on healthy cells. The aim of this study was to assess the possible radiosensitiazation effect of GNPs conjugated with AS1411 aptamer (AS1411/GNPs) on cancer cells treated with 4 MeV electron beams. MATERIALS AND METHODS: Cytotoxicity studies of the GNPs and AS1411/GNPs were carried out with MTT and MTS assay in different cancer cell lines of MCF-7, MDA-MB-231 and mammospheres of MCF-7 cells. Atomic absorption spectroscopy confirmed the cellular uptake of the gold particles. Radiosensitizing effect of the GNPs and AS1411/GNPs on the cancer cells was assessed by clonogenic assay. RESULT: AS1411 aptamer increased the Au uptake in MCF-7 and MDA-MB-231 cells. Clonogenic survival data revealed that AS1411/GNPs at 12.5 mg/L could result in radiosensitization of the breast cancer cells and lead to a sensitizer enhancement ratio of 1.35 and 1.66 and 1.91 for MCf-7, MDA-MB-231 and mammosphere cells. CONCLUSION: Gold nanoparticles delivery to the cancer cells was enhanced by AS1411 aptamer and led to enhanced radiation induced cancer cells death. The combination of our clonogenic assay and Au cell uptake results suggested that AS1411 aptamer has enhanced the radiation-induced cell death by increasing Au uptake. This enhanced sensitization contributed to cancer stem cell-like cells to 4 MeV electron beams. This is particularly important for future preclinical testing to open a new insight for the treatment of cancers.

Time and frequency components of ERG responses in retinitis pigmentosa.

PURPOSE: To evaluate the effects of retinitis pigmentosa (RP) on time, frequency, and time-frequency components of Xenon flash ERG signals using Fourier and wavelet transforms. METHODS: Xenon flash ERG was done in 18 eyes of nine RP patients and 20 normal eyes. After examining latency and amplitude, Fourier and wavelet transforms were performed using MATLAB software. Then, we extracted the mode frequency from the Fourier transform and main frequencies and their occurrence time from the wavelet transform. Finally, mean differences were analyzed using statistical tests. RESULTS: The results indicated increased latency and reduced ERG wave amplitude, no significant inter-group difference in the average mode frequency, and significant reduction in main signal frequencies and their increased occurrence times. Also one or two of the three main frequencies had disappeared in more advanced cases. CONCLUSION: Retinitis pigmentosa can induce changes in ERG time and time-frequency components. Impacted areas can be identified more accurately by wavelet transform and converting scales to frequencies.

Enhancing the effect of 4MeV electron beam using gold nanoparticles in breast cancer cells.

Gold nanoparticles (GNPs) have been applied as radiosensitizer in radiotherapy. Limited reports have shown that GNPs may be effective as a dose enhancer agent for electron radiation therapy. Some Monte Carlo Simulation studies have shown that selecting suitable size of GNPs and electron energies are critical for effective dose enhancement. The aim of this study was to assess possible radiosensitization effect of GNPs on cancer cell treated with 4MeV electron beams. Approximately 10nm GNPs were synthesized and characterized by electron microscope and dynamic light scattering. MCF-7 and MDA-MB-231 breast cancer cells were used and their viability was measured by MTT assay. Radiosensitization effect of GNPs under 4MeV electron beams was measured by clonogenic assay. The result showed a concentration dependent uptake of GNPs without reducing cell viability at concentrations ≤50mg/L. Incubation of cancer cells with GNPs caused a significant decrease in their viability following exposure to electron beams as well as a decrease in their survival fraction when compared to control. The sensitizer enhancement ratio (SER) by electron beams in MCF-7 cells was 1.43 and 1.40 in presence of 25 and 50mg/L GNPs, respectively. For MDA-MB-231 cells, it was 1.62 in presence of 25mg/L GNPs. Our data demonstrated the significant dose enhancement of the GNPs in combination with 4MeV electron beams that could be applicable for the treatment of superficial tumors and intra operative radiation therapy.

Investigation of the gold nanoparticles effects on the prostate dose distribution in brachytherapy: gel dosimetry and Monte Carlo method.

PURPOSE: In this work, gold nanoparticles (GNPs) were embedded in the MAGIC-f polymer gel irradiated with the 192Ir brachytherapy sources. MATERIAL AND METHODS: At the first plexiglas phantom was made as the human pelvis. The GNPs were synthesized with 15 nm in diameter and 0.1 mM (0.0197 mg/ml) in concentration by using a chemical reduction method. Then, the MAGIC-f gel was synthesized. The fabricated gel was poured into the tubes located at the prostate (with and without the GNPs) locations of the phantom. The phantom was irradiated with 192Ir brachytherapy sources for prostate cancer. After 24 hours, the irradiated gels was read by using Siemens 1.5 Tesla MRI scanner. Following the brachytherapy practices, the absolute doses at the reference points and isodose curves were extracted and compared by experimental measurements and Monte Carlo (MC) simulations. RESULTS: The mean absorbed doses in the presence of the GNPs in prostate were 14% higher than the corresponding values without the GNPs in the brachytherapy. The gamma index analysis (between gel and MC) using 7%/7 mm was also applied to the data and a high pass rate achieved (91.7% and 86.4% for analysis with/without GNPs, respectively). CONCLUSIONS: The real three-dimensional analysis shows the comparison of the dose-volume histograms measured for planning volumes and the expected one from the MC calculation. The results indicate that the polymer gel dosimetry method, which developed and used in this study, could be recommended as a reliable method for investigating the dose enhancement factor of GNPs in brachytherapy.

The application of the linear quadratic model to compensate the effects of prolonged fraction delivery time on a Balb/C breast adenocarcinoma tumor: An in vivo study.

Purpose To investigate the effect of increasing the overall treatment time as well as delivering the compensating doses on the Balb/c breast adenocarcinoma (4T1) tumor. Materials and methods A total of 72 mice were divided into two aliquots (classes A and B) based on the initial size of their induced tumor. Each class was divided into a control and several treatment groups. Among the treatment groups, group 1 was continuously exposed to 2 Gy irradiation, and groups 2 and 3 received two subfractions of 1 Gy over the total treatment times of 30 and 60 min, respectively. To investigate the effect of compensating doses, calculated based on the developed linear quadratic model (LQ) model, the remaining two groups (groups 4 and 5) received two subfractions of 1.16 and 1.24 Gy over the total treatment times of 30 and 60 min, respectively. The growing curves, Tumor Growth Time (TGT), Tumor Growth Delay Time (TGDT) and the survival of the animals were studied. Results For class A (tumor size ≤ 30 mm(3)), the average tumor size in the irradiated groups 1-5 was considerably different compared to the control group as one unit (day) change in time, by amount of -160.8, -158.9, +39.4 and +44.0, respectively. While these amounts were +22.0, +17.9, -21.7 and -0.1 for class B (tumor size ≥ 400 mm(3)). For the class A of animals, the TGT and TGDT parameters were significantly lower (0 ≤ 0.05) for the groups 2 and 3, compared to group 1. There was no significant difference (p > 0.05) between groups 1, 4 and 5 in this class. There was no significant difference (p > 0.05) between all the treated groups in class B. Conclusions Increasing total treatment time affects the radiobiological efficiency of treatment especially in small-sized tumor. The compensating doses derived from the LQ model can be used to compensate the effects of prolonged treatment times at in vivo condition.

Comparing the monoisocentric and dual isocentric techniques in chest wall radiotherapy of mastectomy patients.

The monoisocentric (MIT) and dual isocentric (DIT) techniques are compared for the mastectomy patients undergoing chest wall radiotherapy, and a new practical method is suggested for determining the dose calculation reference point to be used in the MIT. Data of 18 mastectomy patients having chest wall radiotherapy were used. To find the appropriate dose calculation reference point for the MIT, the target tissue was divided into nine regions with 17 points as the appropriate candidates. After finding the best reference point for the MIT, dose calculations were made for each patient based on the MIT and DIT to determine the dose distributions of the target volume and organs at risk. The lateral component of the dose calculation reference point was found to be located at one-third of the distance between the geometrical center and the lateral border of the chest wall in the lateral direction toward the outer border. The longitudinal component of this point was found to be located at the geometrical center of the chest wall with a depth located around 2-3 cm under the patients' skin. There was no significant difference between the two radiotherapy planning techniques (MIT and DIT) regarding the dose distributions in the organs at risk and the 95% of the prescribed dose coverage of the target tissue. However, a significant difference for the 105% of the prescribed dose coverage, maximum dose delivered to the target tissue, and the level 2 lymph nodes dose was found, with the DIT showing higher values. Because of the good matching and no superposition observed between the treatment fields in the MIT, it was expected and confirmed that the hot and cold regions (with higher and lower doses than the prescribed dose) with the MIT are significantly fewer than that of the DIT. Therefore, to perform a better conformal radiotherapy for the patients having mastectomy, it could be recommended to use the MIT instead of the DIT and other conventional techniques.

Estimation of cell response in fractionation radiotherapy using different methods derived from linear quadratic model.

BACKGROUND: The aim of this study was to use various theoretical methods derived from the Linear Quadratic (LQ) model to calculate the effects of number of subfractions, time intervals between subfractions, dose per subfraction, and overall fraction time on the cells' survival. Comparison of the results with experimental outcomes of melanoma and breast adenocarcinoma cells was also performed. Finally, the best matched method with experimental outcomes is introduced as the most accurate method in predicting the cell response. MATERIALS AND METHODS: The most widely used theoretical methods in the literature, presented by Keall et al., Brenner, and Mu et al., were used to calculate the cells' survival following radiotherapy with different treatment schemes. The overall treatment times were ranged from 15 to 240 minutes. To investigate the effects of number of subfractions and dose per subfraction, the cells' survival after different treatment delivery scenarios were calculated through fixed overall treatment times of 30, 60 and 240 minutes. The experimental tests were done for dose of 4 Gy. The results were compared with those of the theoretical outcomes. RESULTS: The most affective parameter on the cells' survival was the overall treatment time. However, the number of subfractions per fractions was another effecting parameter in the theoretical models. This parameter showed no significant effect on the cells' survival in experimental schemes. The variations in number of subfractions per each fraction showed different results on the cells' survival, calculated by Keall et al. and Brenner methods (P<0.05). CONCLUSIONS: Mu et al. method can predict the cells' survival following fractionation radiotherapy more accurately than the other models. Using Mu et al. method, as an accurate and simple method to predict the cell response after fractionation radiotherapy, is suggested for clinical applications.

Radioprotective effect of N-acetyl-L-cysteine free radical scavenger on compressive mechanical properties of the gamma sterilized cortical bone of bovine femur.

Gamma sterilization of bone allografts is used as a gold standard method to provide safety against disease transmission. However, it is well documented that high dose levels of ionizing radiation can degrade bone mechanical properties. This effect, which is attributed to the formation of free radicals through radiolysis of the water content of collagen, can lead to post-implantation difficulties such as pre-failure and/or secondary fractures of bone allografts. Recently, treatment of irradiated allografts with free radical scavengers is used to protect them against radiation-induced damages. This study aimed to investigate the radioprotective role of N-acetyl-L-cysteine (NAC) during the gamma sterilization of the cortical bone of bovine femurs using the compressive test. Totally, 195 cubic specimens with a dimension of 5 × 5 × 3 cubic mm were divided into 13 groups including a control and 12 experimental groups exposed to 18, 36, and 70 kGy at three different NAC concentrations (1.25, 12.5, and 25 mM for 18 kGy; 5, 50, and 100 mM for 36 kGy; 10, 100, and 200 mM for 70 kGy). The mechanical behavior of the sterilized specimens was studied using the uniaxial compressive test. The results indicated a concentration-dependent radioprotection effect of NAC on the plastic properties of the cortical bones. The concentration dependency of NAC was in turn related to radiation dose levels. In conclusion, treatment of bone specimens with a characteristic concentration of NAC during exposure to specific radiation dose levels can provide an efficient radioprotection window for preserving the mechanical stability of gamma sterilized allografts.

Radiosensitization effect of folate-conjugated gold nanoparticles on HeLa cancer cells under orthovoltage superficial radiotherapy techniques.

Due to the high atomic number of gold nanoparticles (GNPs), they are known as new radiosensitizer agents for enhancing the efficiency of superficial radiotherapy techniques by increasing the dose absorbed in tumor cells wherein they can be accumulated selectively. The aim of this study was to compare the effect of various common low energy levels of orthovoltage x-rays and megavoltage γ-rays (Co-60) on enhancing the therapeutic efficiency of HeLa cancer cells in the presence of conjugated folate and non-conjugated (pegylated) GNPs. To achieve this, GNPs with an average diameter of 52 nm were synthesized and conjugated to folic acid molecules. Pegylated GNPs with an average diameter of 47 nm were also synthesized and used as non-conjugated folate GNPs. Cytotoxicity assay of the synthesized folate-conjugated and pegylated GNPs was performed using different levels of nanoparticle concentration incubated with HeLa cells for 24 h. The radiosensitizing effect of both the conjugated and pegylated GNPs on the cells at a concentration of 50 µM was compared using MTT as well as clonogenic assays after exposing them to 2 Gy ionizing radiation produced by an orthovoltage x-ray machine at four different kVps and γ-rays of a Co-60 unit. Significant differences were noted among various irradiated groups with and without the folate conjugation, with an average dose enhancement factor (DEF) of 1.64 ± 0.05 and 1.35 ± 0.05 for the folate-conjugated and pegylated GNPs, respectively. The maximum DEF was obtained with the 180 kVp x-ray beam for both of the GNPs. Folate-conjugated GNPs can significantly enhance the cell killing potential of orthovoltage x-ray energies (especially at 180 kVp) in folate receptor-expressing cancer cells, such as HeLa, in superficial radiotherapy techniques.

Effect of gamma sterilization on microhardness of the cortical bone tissue of bovine femur in presence of N-Acetyl-L-Cysteine free radical scavenger.

Gamma sterilization is usually used to minimize the risk of infection transmission through bone allografts. However, it is believed that gamma irradiation affects the mechanical properties of allografts and free radical scavengers can be used to alleviate the radiation-induced degradation of these properties. The aim of this study was to investigate the radioprotective effects of N-Acetyl-L-Cysteine (NAC) free radical scavenger on the material properties of sterilized bovine cortical bone at microstructure level. Forty-two cortical tissue specimens were excised from three bovine femurs and irradiated to 35 and 70 kGy gamma rays in the presence of 5, 50, and 100 mM concentrations of NAC. The localized variations in microhardness were evaluated via indentation in the radial and longitudinal directions to examine different regions of the microstructures of the specimens, including the osteonal and interstitial tissues. A significant increase was observed in the hardness of osteonal, interstitial, and longitudinal combined microstructures exposed to 35 and 70 kGy radiations (P < 0.05), whereas a relative reduction of the hardness was observed in the radial direction. Furthermore, it was found that the application of 50 and 100 mM NAC during gamma irradiation significantly subsided the hardening in longitudinal combined microstructure. Moreover, the reduction of hardness in radial direction was suppressed in the presence of 100 mM of NAC. In conclusion, the results indicated that NAC free radical scavenger can protect the cortical bone against deteriorative effects of ionizing radiation and can be used to improve the material properties of sterilized allografts.

Normal tissue complication probability modeling of radiation-induced hypothyroidism after head-and-neck radiation therapy.

PURPOSE: To determine the dose-response relationship of the thyroid for radiation-induced hypothyroidism in head-and-neck radiation therapy, according to 6 normal tissue complication probability models, and to find the best-fit parameters of the models. METHODS AND MATERIALS: Sixty-five patients treated with primary or postoperative radiation therapy for various cancers in the head-and-neck region were prospectively evaluated. Patient serum samples (tri-iodothyronine, thyroxine, thyroid-stimulating hormone [TSH], free tri-iodothyronine, and free thyroxine) were measured before and at regular time intervals until 1 year after the completion of radiation therapy. Dose-volume histograms (DVHs) of the patients' thyroid gland were derived from their computed tomography (CT)-based treatment planning data. Hypothyroidism was defined as increased TSH (subclinical hypothyroidism) or increased TSH in combination with decreased free thyroxine and thyroxine (clinical hypothyroidism). Thyroid DVHs were converted to 2 Gy/fraction equivalent doses using the linear-quadratic formula with α/ß = 3 Gy. The evaluated models included the following: Lyman with the DVH reduced to the equivalent uniform dose (EUD), known as LEUD; Logit-EUD; mean dose; relative seriality; individual critical volume; and population critical volume models. The parameters of the models were obtained by fitting the patients' data using a maximum likelihood analysis method. The goodness of fit of the models was determined by the 2-sample Kolmogorov-Smirnov test. Ranking of the models was made according to Akaike's information criterion. RESULTS: Twenty-nine patients (44.6%) experienced hypothyroidism. None of the models was rejected according to the evaluation of the goodness of fit. The mean dose model was ranked as the best model on the basis of its Akaike's information criterion value. The D(50) estimated from the models was approximately 44 Gy. CONCLUSIONS: The implemented normal tissue complication probability models showed a parallel architecture for the thyroid. The mean dose model can be used as the best model to describe the dose-response relationship for hypothyroidism complication.

Influence of compensator thickness, field size, and off-axis distance on the effective attenuation coefficient of a cerrobend compensator for intensity-modulated radiation therapy.

Intensity-modulated radiation therapy (IMRT) can be performed by using compensators. To make a compensator for an IMRT practice, it is required to calculate the effective attenuation coefficient (µ(eff)) of its material, which is affected by various factors. We studied the effect of the variation of the most important factors on the calculation of the µ(eff) of the cerrobend compensator for 6-MV photon beams, including the field size, compensator thickness, and off-axis distance. Experimental measurements were carried out at 100 cm source-to-surface distance and 10 cm depth for the 6-MV photon beams of an Elekta linac using various field size, compensator thickness, and off-axis settings. The field sizes investigated ranged from 4 × 4 to 25 × 25 cm² and the cerrobend compensator thicknesses from 0.5-6 cm. For a fixed compensator thickness, variation of the µ(eff) with the field size ranged from 3.7-6.8%, with the highest value attributed to the largest compensator thickness. At the reference field size of 10 × 10 cm², the µ(eff) varied by 16.5% when the compensator thickness was increased from 0.5-6 cm. However, the variation of the µ(eff) with the off-axis distance was only 0.99% at this field size, whereas for the largest field size, it was more significant. Our results indicated that the compensator thickness and field size have the most significant effect on the calculation of the compensator µ(eff) for the 6-MV photon beam. Therefore, it is recommended to consider these parameters when calculating the compensator thickness for an IMRT practice designed for these beams. The off-axis distance had a significant effect on the calculation of the µ(eff) only for the largest field size. Hence, it is recommended to consider the effect of this parameter only for field sizes larger than 25 × 25 cm².

The Cell Survival of F10B16 Melanoma and 4T1 Breast Adenocarcinoma Irradiated to Gamma Radiation Using the MTT Assay Based on Two Different Calculation Methods.

BACKGROUND: various MTT assay methods are proposed to obtain the cell survival parameters. OBJECTIVE: determining the survival curve characteristics of two cancerous cells of interest based on a common and a novel MTT assay method after exposing them to ionizing radiation. METHODS: a common and a novel MTT assay method were used and compared for obtaining the F10B16 melanoma and 4T1 breast adenocarcinoma survivals after exposing them to ionizing radiation from a Co-60 machine. To obtain the survival parameters of the cells based on the common method, the cells were inoculated in 96-well plates. After irradiating the plates, the MTT assay was performed over the following days for a period of 8 days. Thereafter, the survival fraction was calculated from a simple equation for every day from which the best day was selected. To acquire the cells' survival parameters based on the novel method, extensive experiments were performed on a large number of samples. Then, the MTT assay was done in every day following various experimental treatments to acquire the exponential growth. Finally, the cells' survivals were determined by measuring the space between relevant growing curves. RESULTS: at low doses (<4Gy) the two MTT assay methods indicated the same results. However, at higher doses there were significant differences among the findings. CONCLUSION: both of the MTT methods indicated that the cells' responses are dependent on the dose levels used. Although the implementation of the common MTT assay method is simpler, the novel method seems to show more precise and reliable results at all levels of radiation doses.

Evaluation of thyroid disorders during head-and-neck radiotherapy by using functional analysis and ultrasonography.

PURPOSE: To evaluate thyroid function and vascular changes during radiotherapy for patients with head and neck cancer. METHODS AND MATERIALS: Fifty patients treated with primary or postoperative radiotherapy for various cancers in the head and neck region were prospectively evaluated. The serum samples (triiodothyronine [T3], thyroxine [T4], thyroid-stimulating hormone [TSH], free triiodothyronine [FT3], and free thyroxine [FT4]), the echo level of the thyroid gland, and color Doppler ultrasonography (CDU) parameters of the right inferior thyroid artery (RITA) of the patients were measured before and at regular intervals during radiotherapy. The thyroid gland dose-volume histograms of the patients were derived from their computed tomography-based treatment plans. RESULTS: There was a significant fall in TSH level (p < 0.0001) but an increase in FT4 (p < 0.0001) and T4 (p < 0.022) levels during the radiotherapy course. The threshold dose required to produce significant changes was 12 Gy (Biologically Effective Dose in 2-Gy fractions, BED(2)). There were significant rises in the patients' pulsatility index, resistive index, peak systolic velocity, blood volume flow levels, and RITA diameter (p < 0.0001), as detected by CDU during radiotherapy, compared to those parameters measured before the treatment. Hypoechogenicity and irregular echo patterns (p < 0.0001) were seen during radiotherapy compared to those before treatment. There was significant Pearson's correlation between the CDU parameters and T4, FT4, and TSH levels. CONCLUSIONS: Radiation-induced thyroiditis is regarded as primary damage to the thyroid gland. Thyroiditis can subsequently result in hypothyroidism or hyperthyroidism. Our results demonstrated that changes in thyroid vessels occur during radiotherapy delivered to patients. Vessel changes also can be attributed to the late effect of radiation on the thyroid gland. The hypoechogenicity and irregular echo patterns observed in patients may result from the increase in intrathyroidal flow.

Noninvasive prediction of vertebral body compressive strength using nonlinear finite element method and an image based technique.

Noninvasive prediction of vertebral body strength under compressive loading condition is a valuable tool for the assessment of clinical fractures. This paper presents an effective specimen-specific approach for noninvasive prediction of human vertebral strength using a nonlinear finite element (FE) model and an image based parameter based on the quantitative computed tomography (QCT). Nine thoracolumbar vertebrae excised from three cadavers with an average age of 42 years old were used as the samples. The samples were scanned using the QCT. Then, a segmentation technique was performed on each QCT sectional image. The segmented images were then converted into three-dimensional FE models for linear and nonlinear analyses. A new material model was implemented in our nonlinear model being more compatible with real mechanical behavior of trabecular bone. A new image based MOS (Mechanic of Solids) parameter named minimum sectional strength ((sigma(u)A)(min)) was used for the ultimate compressive strength prediction. Subsequently, the samples were destructively tested under uniaxial compression and their experimental ultimate compressive strengths were obtained. Results indicated that our new implemented FE model can predict ultimate compressive strength of human vertebra with a correlation coefficient (R(2)=0.94) better than usual linear and nonlinear FE models (R(2)=0.83 and 0.85 respectively). The image based parameter introduced in this study ((sigma(u)A)(min)) was also correlated well with the experimental results (R(2)=0.86). Although nonlinear FE method with new implemented material model predicts compressive strength better than the (sigma(u)A)(min), this parameter is clinically more feasible due to its simplicity and lower computational costs. This can make future applications of the (sigma(u)A)(min) more justified for human vertebral body compressive strength prediction.