T Marques

Gel Dosimetry Analysis of Gold Nanoparticle Application in Kilovoltage Radiation Therapy

In this work gold nanoparticles (AuNP) were embedded in MAGIC-f gel and irradiated in a 250 kV x-ray clinical beam. The signal of non-irradiated gel samples containing AuNPs showed maximum difference of 0.5% related to gel without nanoparticles. Different AuNPs concentrations were studied: 0.10 mM, 0.05 mM and 0.02 mM, presenting dose enhancements of 106%, 90% and 77% respectively. Monte Carlo spectrometry was performed to quantify theoretical changes in photon energy spectrums due to AuNPs presence. Concordance between simulated dose enhancements and gel dosimetry measurements was better than 97% to all concentrations studied. This study evidences that polymer gel dosimetry as a suitable tool to perform dosimetric investigations of nanoparticle applications in Radiation Therapy.

Association of genetic variants in the promoter region of genes encoding p22phox (CYBA) and glutamate cysteine ligase catalytic subunit (GCLC) and renal disease in patients with type 1 diabetes mellitus

BackgroundOxidative stress is recognized as a major pathogenic factor of cellular damage caused by hyperglycemia. NOX/NADPH oxidases generate reactive oxygen species and NOX1, NOX2 and NOX4 isoforms are expressed in kidney and require association with subunit p22phox (encoded by the CYBA gene). Increased expression of p22phox was described in animal models of diabetic nephropathy. In the opposite direction, glutathione is one of the main endogenous antioxidants whose plasmatic concentrations were reported to be reduced in diabetes patients. The aim of the present investigation was to test whether functional single nucleotide polymorphisms (SNPs) in genes involved in the generation of NADPH-dependent O2•- (-675 T → A in CYBA, unregistered) and in glutathione metabolism (-129 C → T in GCLC [rs17883901] and -65 T → C in GPX3 [rs8177412]) confer susceptibility to renal disease in type 1 diabetes patients.Methods401 patients were sorted into two groups according to the presence (n = 104) or absence (n = 196) of overt diabetic nephropathy or according to glomerular filtration rate (GFR) estimated by Modification of Diet in Renal Disease (MDRD) equation: ≥ 60 mL (n = 265) or < 60 mL/min/1.73 m2 (n = 136) and were genotyped.ResultsNo differences were found in the frequency of genotypes between diabetic and non-diabetic subjects. The frequency of GFR < 60 mL/min was significantly lower in the group of patients carrying CYBA genotypes T/A+A/A (18.7%) than in the group carrying the T/T genotype (35.3%) (P = 0.0143) and the frequency of GFR < 60 mL/min was significantly higher in the group of patients carrying GCLC genotypes C/T+T/T (47.1%) than in the group carrying the C/C genotype (31.1%) (p = 0.0082). Logistic regression analysis identified the presence of at least one A allele of the CYBA SNP as an independent protection factor against decreased GFR (OR = 0.38, CI95% 0.14-0.88, p = 0.0354) and the presence of at least one T allele of the GCLC rs17883901 SNP as an independent risk factor for decreased GFR (OR = 2.40, CI95% 1.27-4.56, p = 0.0068).ConclusionsThe functional SNPs CYBA -675 T → A and GCLC rs17883901, probably associated with cellular redox imbalances, modulate the risk for renal disease in the studied population of type 1 diabetes patients and require validation in additional cohorts.

Association of single nucleotide polymorphisms in the gene encoding GLUT1 and diabetic nephropathy in Brazilian patients with type 1 diabetes mellitus

Mesangial cells subject to high extracellular glucose concentrations, as occur in hyperglycaemic states, are unable to down regulate glucose influx, resulting in intracellular activation of deleterious biochemical pathways. A high expression of GLUT1 participates in the development of diabetic glomerulopathy. Variants in the gene encoding GLUT1 (SLC2A1) have been associated to this diabetic complication. The aim of this study was to test whether polymorphisms in SLC2A1 confer susceptibility to diabetic nephropathy (DN) in Brazilian type 1 diabetes patients. Four polymorphisms (rs3820589, rs1385129, rs841847 and rs841848) were genotyped in a Brazilian cohort comprised of 452 patients. A prospective analysis was performed in 155 patients. Mean duration of follow-up was 5.6 ± 2.4 years and the incidence of renal events was 18.0%. The rs3820589 presented an inverse association with the prevalence of incipient DN (OR: 0.36, 95% CI: 0.16 - 0.80, p=0.01) and with progression to renal events (HR: 0.20; 95% CI: 0.03 - 0.70; p=0.009). AGGT and AGAC haplotypes were associated with the prevalence of incipient DN and the AGAC haplotype was also associated with the prevalence of established/advanced DN. In conclusion, rs3820589 in the SLC2A1 gene modulates the risk to DN in Brazilian patients with inadequate type 1 diabetes control.

Dosimetric properties of MAGIC-f polymer gel assessed to Radiotherapy clinical beams

Dosimetric properties of MAGIC-f gel were studied for a wide range of beams used in Radiotherapy. The MAGIC-f tissue-equivalence was theoretically verified using PENELOPE Monte Carlo code and experimentally by percentage depth dose curves for water and gel (maximum differences of 2.0% and 0.5% for 6MV and 10MV, respectively). Energy and dose-rate dependency were evaluated in a range from 60 kV to 10 MV and 0.44 Gy/min to 10 Gy/min respectively. MAGIC-f presents linearity to all energies studied and its sensitivity presents maximum and average variation of 8.6% and 7.7% respectively in the range of energy considered. The study of dose rate dependency evidence that MAGIC-f presents no significant variation of response in clinical intervals of dose rate: lower than 0.7% when x-ray are considered and lower than 1.9% when all beams are considered. Its dosimetric characteristics indicate that MAGIC-f is a very suitable dosimeter for Radiotherapy.

MAGIC with formaldehyde applied to dosimetry of HDR brachytherapy source

The use of polymer gel dosimeters in brachytherapy can allow the determination of three-dimensional dose distributions in large volumes and with high spatial resolution if an adequate calibration process is performed. One of the major issues in these experiments is the polymer gel response dependence on dose rate when high dose rate sources are used and the doses in the vicinity of the sources are to be determinated. In this study, the response of a modified MAGIC polymer gel with formaldehyde around an Iridium-192 HDR brachytherapy source is presented. Experimental results obtained with this polymer gel were compared with ionization chamber measurements and with Monte Carlo simulation with PENELOPE. A maximum difference of 3.10% was found between gel dose measurements and Monte Carlo simulation at a radial distance of 18 mm from the source. The results obtained show that the gels response is strongly influenced by dose rate and that a different calibration should be used for the vicinity of the source and for regions of lower dose rates. The results obtained in this study show that, provided the proper calibration is performed, MAGIC with formaldehyde can be successfully used to accurate determinate dose distributions form high dose rate brachytherapy sources.

Redução de incertezas em radioterapia utilizando simulação Monte Carlo: análise espectral aplicada à correção de dose absorvida

OBJETIVO: Determinar, por simulacao Monte Carlo, os espectros de feixes de cobaltoterapia em profundidade na agua e fatores de correcao para doses absorvidas em dosimetros termoluminescentes de fluoreto de litio. MATERIAIS E METODOS: As simulacoes dos espectros secundarios da fonte clinica de cobalto-60 foram realizadas com o codigo Monte Carlo PENELOPE, em diversas profundidades na agua. Medidas experimentais de dose profunda foram obtidas com dosimetros termoluminescentes e câmara de ionizacao em condicoes de referencia em radioterapia. Os fatores de correcao para os dosimetros termoluminescentes foram obtidos atraves da razao entre as absorcoes relativas ao espectro de baixa energia e ao espectro total. RESULTADOS: A analise espectral em profundidade revelou a existencia de espectros secundarios de baixa energia responsaveis por uma parcela significativa da deposicao de dose. Foram observadas discrepâncias de 3,2% nas doses medidas experimentalmente com a câmara de ionizacao e com os dosimetros termoluminescentes. O uso dos fatores de correcao nessas medidas permitiu diminuir a discrepância entre as doses absorvidas para, no maximo, 0,3%. CONCLUSAO: Os espectros simulados permitem o calculo de fatores de correcao para as leituras de dosimetros termoluminescentes utilizados em medidas de dose profunda, contribuindo para a reducao das incertezas associadas ao controle de qualidade de feixes clinicos em radioterapia.

Benefits of Radiotherapy Added Nanoparticle Assessed by a Quantitative Analysis of Dose-Gradient: An Evaluation in Soft and Lung Tissues by Monte Carlo

Purpose: Evaluate the volume fraction enclosed by maximum isodose (isodosemax) within a structure as a quantitative criterion for assessing the benefits of using nanoparticles in Radiotherapy.Material and Methods:Dose enhancement can be evaluated in a volume with and without nanoparticles by the ratio between mean doses, defining an average‐dose‐enhancement‐factor (DEF). Decompounding DEF in multiplicative terms is possible to define a maximum‐dose‐enhancement‐factor(DEFmax) and a dose‐gradient‐factor(GF). GF express what fraction of volume is enclosed by the isodosemax present in the analyzed structure. GF close to 1 express that the isodosemax present in the analyzed volume increase its value. GF close to 0 indicates that the isodosemax decrease its value. Soft and lung targets with 3×3×1cm3 containing and not containing 0.11mM concentration of goldnanoparticles (AuNP) were considered to Monte Carlo simulations, performed with PENELOPE‐2008. Adjacent‐volumes were delimited as tissues 1cm far from the target in all directions. A 120kV x‐ray beam was considered to simulate Intra‐Operative‐Radiotherapy situations. Results:Dose distributions visually revels changes in dose‐gradient and depth dose curves presents it quantitatively. In target soft tissue: DEF soft‐tissue target = 2.44 and DEF max soft‐tissue target = 2.40; To adjacent‐volume DEF soft‐tissue adjacent volume = 1.14 and max soft‐tissue adjacent volume = 2.44. It indicates that in target isodose max changes not so much, presenting almost the same values in situations with and without AuNP; However in adjacent‐volume isodosemax had its value increased. In target lung tissue: DEF lung‐tissue target = 2.43 ; DEF max lung‐tissue target = 2.49; DEF lung‐tissue adjacent volume = 0.92; DEF max lung‐tissue adjacent volume = 2.30. These parameters indicate that the isodosemax changes its value not so much in lung‐target but radically in lung‐adjacent‐tissue. This behavior is expressed in each corresponding GF of these structures: GF soft‐tissue target = 1.02; GF soft‐tissue adjacent volume = 0.47; GF lung‐tissue target = 0.97; GF lung‐tissue adjacent volume = 0.39. Coclusions: AuNP increase the mean dose in target and decrease radically the maximum isodose in adjacent tissues. The GF express quantitatively how attenuation and dose‐contribution effects are balanced providing information to guide clinical cases of nanoparticle added to Radiotherapy.

SU‐E‐T‐145: MRI Gel Dosimetry Applied to Dose Profile Determination for 50kV X‐Ray Tube

PURPOSE The aim of this study was to use MRI gel dosimetry to determine the dose profile of 50kV MAGNUM® X-ray tube, MOXTEK Inc., in order to calibrate small solid dosimeters of alanine, tooth enamel and LiF-TLDs, commonly used in clinical quality assurance and datation dosimetry. METHODS MAGIC-f polymer gel was kept in two plastic containers of 100mL, avoiding attenuation of the primary beam trough the wall. Beam aberture of 3mm and dose rate of 16.5Gy/min were set, reproducing irradiation conditions of interest. The dose rate was assumed based on data of the vendor information of the tube and dose of 30Gy was delivered at the surface of the gel. MAGIC-f gel was irradiated at source-surface distances(SSD) of 0.1cm and 1.0cm. After 24hours of irradiation, gel was scanned in an Achieva® 3T Philips® MRI tomography using relaxometry sequence with 32 Echos, Time-to-Echo(TE) of 15.0ms, Time-to-Repetition(TR) of 6000ms and Field-of-View(FOV) of 0.5×0.5×2.0mm. Dose map at the central plain of irradiation was calculated from T2 relaxometry map. RESULTS The gel dosimetry results evidenced a build-up depth of 0.13cm for SSD=0.1cm and no build-up was detected for SSD=1.0cm. However, the dose profile evidenced high gradient of dose in SSD=0.1, decreasing the dose from 100% to 30% in 1.4cm depth inside the gel; In turn, the dose distribution is homogeneous after 0.4cm deth for SSD=1.0cm. CONCLUSIONS MRI gel dosimetry using MAGIC-f presented as feasible technique to determine dose profiles for kilovoltage x-rays tubes. The results evidenced that the calibration of small solid dosimeters can be performed using SSD of 1.0cm in the 50kV MAGNUM® X-ray tube using 0.4cm/g/cm3 filter. This work was funded supported by CNPQ, CAPES and FAPESP.

SU‐E‐T‐462: Microscopic Fractions of Dose Enhancement: Size Dependence Study to Gold Nanoparticle Using Monte Carlo

Purpose: To quantitatively compare fractions of dose enhancement in microscopic ranges (m‐DEF) due to goldnanoparticles (AuNP) with different sizes using Monte Carlo simulation. Material and Methods: PENELOPE Monte Carlo code was used to perform simulations of dose deposition. The history condensation parameters of the event‐by‐event electron simulations were set as 0.05 maximum fraction of energy loss and 0.05 maximum fraction of angular deviation per interaction. Two clinical energy spectrums were considered in this study: Ir‐192 HDR brachytherapy source and 200kV ortovoltage beam. Six AuNP spherical sizes were simulated from 10nm to 150nm. Nanoparticles were positioned inside a virtual 8μm spherical cell and total gold concentration was 0.01% mass fraction. Doses were recorded inside the cell and m‐DEFs were calculated as the ratio between total dose deposited inside the cell with and without nanoparticles. Results: A non‐linear relation was found between nanoparticle size and m‐DEF to both clinical beams considered. The m‐DEF found to 50nm particles enclosed to the cell in 200kV and Ir‐192 simulations were 1.73 and 1.56, respectively. This value becomes lower than 1.20 when 150nm nanoparticles are considered to both energy beams. When particles in a range from 10nm to 40nm are considered, the m‐DEF found was lower than 1.40, being higher to 200kV beam. Standard deviations are around 5% to 10nm simulations and decreases fast with particle size, reaching 1% to 150nm AuNP particles. Conclusions: Microscopic dose enhancement fractions are dependent to goldnanoparticle size and this relation can be studied by Monte Carlo when properly statistical analysis is applied. An optimized size of goldnanoparticle can be determined according to radiation therapy beam of interest. The size dependence of m‐DEF has its origin in the range of the electrons created inside the AuNPs that delivery doses inside the cells, being more expressive to large sizes.

SU-E-T-340: Dose Enhancement Due to Backscattered Electrons of Gold Nanoparticle: Size and Shape Dependency Study by Thermoluminescent Dosimetry

Purpose: Quantify dose enhancement fractions (DEF) caused by backscatteredelectrons of goldnanoparticles with different size and shape using thermoluminescent dosimeters(TLD). Methods: Goldnanorods (AuNP‐rod) of 45nm and spherical goldnanoparticles (AuNP) of 5nm average diameter were used in this study. Fourteen Lithium Fluoride TLDs (LiF‐100) groups were pre‐calibrated in the 200kV x‐ray beam studied. Different mass‐fractions of gold (0%, 0.1%, 0.2%, 0.3%, 0.5%, 0.7% and 0.8%) were casted only in one surface of each tablet. An acrylic plate with a small recess properly designed to fit tablets of a same group each time; 10cm of acrylic were also positioned down the TLDs to guarantee backscattering conditions. 2Gy were delivered to all groups. The AuNPs films were down positioned related to the beam incidence during the experiments aiming to measure backscatteredelectrons of AuNPs. TLDs were positioned in two depths: surface and build‐up. DEF was calculated as the ratio between dose measured with TLD tablets with and without AuNP. Results: Experimental DEF varies between 1 and 1.26 to both AuNP‐rods and AuNPs when positioned on the surface. At the build‐up depth the experimental DEFs found were 1, 1.02, 1.04, 1.09, 1.12, 1.16 and 1.17 respectively to concentrations 0%, 0.1%, 0.2%, 0.3%, 0.5%, 0.7% and 0.8% of AuNP‐rods; To the same gold concentrations of spherical nanoparticles the DEFs found were 1, 1.02, 1.02, 1.03, 1.04, 1.08 and 1.11. A linear behavior between gold concentration casted and DEFs measured was observed to both depths of irradiation. Conclusions: Differences of 6% in fractions of dose enhancements can be found when 45nm AuNP‐rods and 5nm spherical AuNPs are considered. The angular distribution of scatteredelectrons in AuNP combined to nanoparticle size and shape implies in its self attenuation inside the nanoparticles and thereof the fractions of dose enhancements around the particles.