Gadolinium-Based Nanoparticles Sensitize Ovarian Peritoneal Carcinomatosis to Targeted Radionuclide Therapy.

Ovarian cancer (OC) is the most lethal gynecologic malignancy (5-y overall survival rate, 46%). OC is generally detected when it has already spread to the peritoneal cavity (peritoneal carcinomatosis). This study investigated whether gadolinium-based nanoparticles (Gd-NPs) increase the efficacy of targeted radionuclide therapy using [177Lu]Lu-DOTA-trastuzumab (an antibody against human epidermal growth factor receptor 2). Gd-NPs have radiosensitizing effects in conventional external-beam radiotherapy and have been tested in clinical phase II trials. Methods: First, the optimal activity of [177Lu]Lu-DOTA-trastuzumab (10, 5, or 2.5 MBq) combined or not with 10 mg of Gd-NPs (single injection) was investigated in athymic mice bearing intraperitoneal OC cell (human epidermal growth factor receptor 2-positive) tumor xenografts. Next, the therapeutic efficacy and toxicity of 5 MBq of [177Lu]Lu-DOTA-trastuzumab with Gd-NPs (3 administration regimens) were evaluated. NaCl, trastuzumab plus Gd-NPs, and [177Lu]Lu-DOTA-trastuzumab alone were used as controls. Biodistribution and dosimetry were determined, and Monte Carlo simulation of energy deposits was performed. Lastly, Gd-NPs' subcellular localization and uptake, and the cytotoxic effects of the combination, were investigated in 3 cancer cell lines to obtain insights into the involved mechanisms. Results: The optimal [177Lu]Lu-DOTA-trastuzumab activity when combined with Gd-NPs was 5 MBq. Moreover, compared with [177Lu]Lu-DOTA-trastuzumab alone, the strongest therapeutic efficacy (tumor mass reduction) was obtained with 2 injections of 5 mg of Gd-NPs/d (separated by 6 h) at 24 and 72 h after injection of 5 MBq of [177Lu]Lu-DOTA-trastuzumab. In vitro experiments showed that Gd-NPs colocalized with lysosomes and that their radiosensitizing effect was mediated by oxidative stress and inhibited by deferiprone, an iron chelator. Exposure of Gd-NPs to 177Lu increased the Auger electron yield but not the absorbed dose. Conclusion: Targeted radionuclide therapy can be combined with Gd-NPs to increase the therapeutic effect and reduce the injected activities. As Gd-NPs are already used in the clinic, this combination could be a new therapeutic approach for patients with ovarian peritoneal carcinomatosis.

Implementation of dose point kernel (DPK) for dose optimization of 177Lu/90Y cocktail radionuclides in internal dosimetry.

BACKGROUND: Due to the importance of choosing the applicable dosimetry method in radionuclide therapy, the present study was conducted to investigate the efficiency of the implementation of Dose Point Kernel (DPK) for dose optimization of 177Lu/90Y Cocktail Radionuclides in internal Dosimetry. METHODS: In this study, simulations and calculations of DPK were performed using the GATE/GEANT4 Monte Carlo code. For specific liver dosimetry, the NCAT phantom and convolution algorithm-based Fast Fourier Transform method was used by MATLAB software. RESULTS: The self-dose of 177Lu and 90Y radionuclides in the liver of NCAT phantom were 1.1708E-13, and 4.8420E-11 (Gy/Bq), respectively, and the cross-dose of 177Lu and 90Y radionuclides out of the liver of NCAT phantom were 2.03615E-16, and 0.8422E-13 (Gy/Bq) respectively. Overall results showed that with an increase the value of 90Y with quarter steps in a cocktail, the amount of the self-dose increase 1.5, 6, and 29 times respectively, and with an increase the value of 177Lu in quarter step in a cocktail, the amount of the cross dose decrease 3, 15 and 68 percent respectively. CONCLUSION: Generally, the present results indicate that the calculated DPK functions of 177Lu and 90Y cocktails can play an important role in choosing the best combination of radionuclide to optimize treatment planning in cocktail radionuclide therapy.

Data on biodistribution and dose calculation of 99mTechnetium -Dimercaptosuccinic acid in pediatric patients using a hybrid planar/single emission computed tomography method.

The Biodistribution and absorbed dose data from the administration of radiopharmaceuticals are necessary to analyze the risk-benefit of the procedure. It has particular significance in children, as their metabolism is very different from adults. 99mTc-DMSA scintigraphy is the golden standard imaging technique for the assessment of renal involvement in febrile urinary tract infection and renal sequels. However, 99mTc-DMSA biodistribution data for children are scarce and usually outdated which have been obtained by older methods. In this data article, we analysed the biodistribution of 99mTc-DMSA in 12 pediatric patients using planar/SPECT method. In addition, the radiation absorbed doses were calculated by MIRDOSE software.

Occupational eye dose to medical staff in various interventional cardiologic procedures: is the need for lead goggles the same in all groups of radiation workers?

Considering the increased use of interventional cardiologic procedures and concern about irradiation to the eyes, it is necessary to measure eye dose in radiation workers. The assessment of eye dose using collar dose is a routine but inaccurate method. Therefore this study was designed to measure eye dose in the radiation workers of various interventional cardiologic procedures. In this study eye dose was measured for left and right eyes in three groups of radiation workers in angiography ward of Afshar hospital in various procedures using TLD. Measurements were done separately for cardiologists, nurses and radio-technologists in 100 procedures. The nurses functioned as surgical assistants and were usually close to the table. The correlation of staff dose to exposure parameters was also investigated. Eye dose in physicians were higher than other staff in all procedures. Also the left eye dose was considerably higher than right one, especially for physicians. The median equivalent dose per procedure of left eye for physicians, nurses and radio-technologists were 7.4, 3.6, 1.4 µSv (PCI) and 3.2, 3.1, 1.3 µSv (Adhoc) and 3.2, 1.7, 1.1 µSv (CA), respectively. The annual left eye equivalent dose with (without) using lead goggles were 2.4 (15.3), 1.4 (2.2), 1.0 (1.1) mSv for physicians, nurses and radio-technologists, respectively. There were also a positive correlation between eye dose and KAP for procedures without lead goggles. The lead goggles showed lower protection effects for radio-technologists than other staff. Only 30% of physicians received a dose higher than 1/3 of the ICRP annual dose limit, therefor only physician eye dose should be monitored in catheterization labs.

PATIENT-SPECIFIC DOSIMETRY FOR PEDIATRIC IMAGING OF 99mTc-DIMERCAPTOSUCCINIC ACID WITH GATE MONTE CARLO CODE.

In this study, radiation absorbed dose of 99mTc-dimercaptosuccinic acid (DMSA) in critical organs was calculated using Monte Carlo simulation. Ten child patients with genitourinary abnormalities were imaged using a series of planar, SPECT and MRI, after injection with 99mTc-DMSA. Patient-specific organ segmentation was performed on MRI and used as input in GATE. Organs with substantial uptake included kidneys, bladder and liver. The mean organ absorbed dose coefficients (mGy/MBq) were 0.063, 0.058, 0.018, 0.016, 0.013 and 0.010 for the right kidney, left kidney, bones, urinary bladder wall, liver and gonads, respectively. The absorbed dose coefficients in the remainder of the body was 0.012 mGy/MBq. The authors implemented an image-based Monte Carlo method for patient-specific 3D absorbed dose calculation. This study also demonstrates the possibility to obtain patient-specific attenuation map from MRI to be used for the simulations of radiation transport and energy deposition in phantom using Monte Carlo methods.

Specific Absorbed Fractions of Internal Photon and Electron Emitters in a Human Voxel-based Phantom: A Monte Carlo Study.

The specific absorbed fraction (SAF) of energy is an essential element of internal dose assessment. Here reported a set of SAFs calculated for selected organs of a human voxel-based phantom. The Monte Carlo transport code GATE version 6.1 was used to simulate monoenergetic photons and electrons with energies ranging from 10 keV to 2 MeV. The particles were emitted from three source organs: kidneys, liver, and spleen. SAFs were calculated for three target regions in the body (kidneys, liver, and spleen) and compared with the results obtained using the MCNP4B and GATE/GEANT4 Monte Carlo codes. For most photon energies, the self-irradiation is higher, and the cross-irradiation is lower in the GATE results compared to the MCNP4B. The results show generally good agreement for photons and high-energy electrons with discrepancies within - 2% ±3%. Nevertheless, significant differences were found for cross-irradiation of photons of lower energy and electrons of higher energy due to statistical uncertainties larger than 10%. The comparisons of the SAF values for the human voxel phantom do not show significant differences, and the results also demonstrated the usefulness and applicability of GATE Monte Carlo package for voxel level dose calculations in nonuniform media. The present SAFs calculation for the Zubal voxel phantom is validated by the intercomparison of the results obtained by other Monte Carlo codes.

The importance of BMI in dosimetry of 153Sm-EDTMP bone pain palliation therapy: A Monte Carlo study.

Using digital phantoms as an atlas compared to acquiring CT data for internal radionuclide dosimetry decreases patient overall radiation dose and reduces the required analysis effort and time for organ segmentation. The drawback is that the phantom may not match exactly with the patient. We assessed the effect of varying BMIs on dosimetry results for a bone pain palliation agent, 153Sm-EDTMP. The simulation was done using the GATE Monte Carlo code. Female XCAT phantoms with the following different BMIs were employed: 18.6, 20.8, 22.1, 26.8, 30.3 and 34.7kg/m2. S-factors (mGy/MBq.s) and SAFs (kg-1) were calculated for the dosimetry of the radiation from major source organs including spine, ribs, kidney and bladder into different target organs as well as whole body dosimetry from spine. The differences in dose estimates from different phantoms compared to those from the phantom with BMI of 26.8kg/m2 as the reference, were calculated for both gamma and beta radiations. The relative differences (RD) of the S-factors or SAFs from the values of reference phantom were calculated. RDs greater than 10% and 100% were frequent in radiations to organs for photon and beta particles, respectively. The relative differences in whole body SAFs from the reference phantom were 15.4%, 7%, 4.2%, -9.8% and -1.4% for BMIs of 18.6, 20.8, 22.1, 30.3 and 34.7kg/m2, respectively. The differences in whole body S-factors for the phantoms with BMIs of 18.6, 20.8, 22.1, 30.3 and 34.7kg/m2 were 39.5%, 19.4%, 8.8%, -7.9% and -4.3%, respectively. The dosimetry of the gamma photons and beta particles changes substantially with the use of phantoms with different BMIs. The change in S-factors is important for dose calculation and can change the prescribed therapeutic dose of 153Sm-EDTMP. Thus a phantom with BMI better matched to the patient is suggested for therapeutic purposes where dose estimates closer to those in the actual patient are required.

Internal dosimetry for radioembolization therapy with Yttrium-90 microspheres.

The absorbed doses in the liver and adjacent viscera in Yttrium-90 radioembolization therapy for metastatic liver lesions are not well-documented. We sought for a clinically practical way to determine the dosimetry of this advent treatment. Six different female XCAT BMIs and seven different male XCAT BMIs were generated. Using Monte Carlo GATE code simulation, the total of 100MBq 90 Y was deposited uniformly in the source organ, liver. Self-irradiation and absorbed doses in lung, kidney and bone marrow were calculated. The mean energy of Yittrium-90 (i.e., 0.937 MeV) was used. The S-values and equivalent doses in target organs were estimated. The dose absorbed in the liver was between 84 and 53 Gy and below the target of 80 to 150 Gy. The absorbed dose in the bone marrow, lungs, and kidneys are very low and below 0.1 , 0.4, and 0.5 Gy respectively. Our study indicates that larger activities than the conventional dose of 3 GBq may be both required and safe. Further confirmations in clinical settings are needed.

Practical Nuclear Medicine and Utility of Phantoms for Internal Dosimetry: XCAT Compared with Zubal.

PURPOSE: The absorbed doses for two radioisotopes, 99mTc and 131I, between previously validated Zubal phantom and the recently developed XCAT phantom were compared. MATERIALS AND METHODS: GATE Monte Carlo code was used to simulate the statistical process of radiation. A XCAT phantom with voxel and matrix sizes similar to a standard Zubal phantom was generated. According to Medical International Radiation Dose formalism, specific absorbed fraction (SAF) values for photons and S-factors for beta particles were tabulated. The amounts of absorbed doses were calculated and compared in different organs. RESULTS: The differences of gamma radiation doses, SAFs, between Zubal and XCAT are >50% in adrenal from adrenal, pancreas from pancreas and thyroid from thyroid, in lung from kidney, kidneys from lungs and in kidneys from thyroid and thyroid from kidneys. The beta radiation doses differences between Zubal and XCAT are >50% in thyroid from thyroid, bladder from bladder, kidney from kidney, liver from bladder, thyroid from bladder and kidney from thyroid. The size and distances of the organs were different between XCAT and Zubal phantoms. Denoted differences of SAF and S-factors correspond to the different organ geometries in phantoms. CONCLUSION: The results of absorbed doses in Zubal and XCAT phantoms are different. The variations prohibit easy comparison or interchangeability of dosimetry between these phantoms.

A 3D Monte Carlo Method for Estimation of Patient-specific Internal Organs Absorbed Dose for (99m)Tc-hynic-Tyr(3)-octreotide Imaging.

Single-photon emission computed tomography (SPECT)-based tracers are easily available and more widely used than positron emission tomography (PET)-based tracers, and SPECT imaging still remains the most prevalent nuclear medicine imaging modality worldwide. The aim of this study is to implement an image-based Monte Carlo method for patient-specific three-dimensional (3D) absorbed dose calculation in patients after injection of (99m)Tc-hydrazinonicotinamide (hynic)-Tyr(3)-octreotide as a SPECT radiotracer. (99m)Tc patient-specific S values and the absorbed doses were calculated with GATE code for each source-target organ pair in four patients who were imaged for suspected neuroendocrine tumors. Each patient underwent multiple whole-body planar scans as well as SPECT imaging over a period of 1-24 h after intravenous injection of (99m)hynic-Tyr(3)-octreotide. The patient-specific S values calculated by GATE Monte Carlo code and the corresponding S values obtained by MIRDOSE program differed within 4.3% on an average for self-irradiation, and differed within 69.6% on an average for cross-irradiation. However, the agreement between total organ doses calculated by GATE code and MIRDOSE program for all patients was reasonably well (percentage difference was about 4.6% on an average). Normal and tumor absorbed doses calculated with GATE were slightly higher than those calculated with MIRDOSE program. The average ratio of GATE absorbed doses to MIRDOSE was 1.07 ± 0.11 (ranging from 0.94 to 1.36). According to the results, it is proposed that when cross-organ irradiation is dominant, a comprehensive approach such as GATE Monte Carlo dosimetry be used since it provides more reliable dosimetric results.

Monte Carlo and experimental internal radionuclide dosimetry in RANDO head phantom.

Monte Carlo techniques are widely employed in internal dosimetry to obtain better estimates of absorbed dose distributions from irradiation sources in medicine. Accurate 3D absorbed dosimetry would be useful for risk assessment of inducing deterministic and stochastic biological effects for both therapeutic and diagnostic radiopharmaceuticals in nuclear medicine. The goal of this study was to experimentally evaluate the use of Geant4 application for tomographic emission (GATE) Monte Carlo package for 3D internal dosimetry using the head portion of the RANDO phantom. GATE package (version 6.1) was used to create a voxel model of a human head phantom from computed tomography (CT) images. Matrix dimensions consisted of 319 × 216 × 30 voxels (0.7871 × 0.7871 × 5 mm(3)). Measurements were made using thermoluminescent dosimeters (TLD-100). One rod-shaped source with 94 MBq activity of (99m)Tc was positioned in the brain tissue of the posterior part of the human head phantom in slice number 2. The results of the simulation were compared with measured mean absorbed dose per cumulative activity (S value). Absorbed dose was also calculated for each slice of the digital model of the head phantom and dose volume histograms (DVHs) were computed to analyze the absolute and relative doses in each slice from the simulation data. The S-values calculated by GATE and TLD methods showed a significant correlation (correlation coefficient, r(2) ≥ 0.99, p < 0.05) with each other. The maximum relative percentage differences were ≤14% for most cases. DVHs demonstrated dose decrease along the direction of movement toward the lower slices of the head phantom. Based on the results obtained from GATE Monte Carlopackage it can be deduced that a complete dosimetry simulation study, from imaging to absorbed dose map calculation, is possible to execute in a single framework.

Paired organs-should they be treated jointly or separately in internal dosimetry?

PURPOSE: Size, shape, and the position of paired organs are different in abdomen. However, the counterpart organs are conventionally treated jointly together in internal dosimetry. This study was performed to quantify the difference of specific absorbed fraction of organs in considering paired organs jointly like single organs or as two separate organs. METHODS: Zubal phantom and GATE Monte Carlo package were used to calculate the SAF for the self-absorption and cross-irradiation of the lungs, kidneys, adrenal glands (paired organs), liver, spleen, stomach, and pancreas (single organs). The activity was assumed uniformly distributed in the organs, and simulation was performed for monoenergetic photons of 10, 50, 100, 500, 1000 keV and mono-energetic electrons of 350, 500, 690, 935, 1200 keV. RESULTS: The results demonstrated that self-absorption of left and right counterpart organs may be different depending upon the differences in their masses. The cross-irradiations between left-to-right and right-to-left counterpart organs are always equal irrespective of difference in their masses. Cross-irradiation from the left and right counterpart organs to other organs are different (4-24 times in Zubal phantom) depending on the photon energy and organs. The irradiation from a single source organ to the left and right counterpart paired organs is always different irrespective of activity concentration. CONCLUSIONS: Left and right counterpart organs always receive different absorbed doses from target organs and deliver different absorbed doses to target organs. Therefore, in application of radiopharmaceuticals in which the dose to the organs plays a role, counterpart organs should be treated separately as two separate organs.© 2011 American Association of Physicists in Medicine.

Assessment of MIRD data for internal dosimetry using the GATE Monte Carlo code.

GATE/GEANT is a Monte Carlo code dedicated to nuclear medicine that allows calculation of the dose to organs of voxel phantoms. On the other hand, MIRD is a well-developed system for estimation of the dose to human organs. In this study, results obtained from GATE/GEANT using Snyder phantom are compared to published MIRD data. For this, the mathematical Snyder phantom was discretized and converted to a digital phantom of 100 × 200 × 360 voxels. The activity was considered uniformly distributed within kidneys, liver, lungs, pancreas, spleen, and adrenals. The GATE/GEANT Monte Carlo code was used to calculate the dose to the organs of the phantom from mono-energetic photons of 10, 15, 20, 30, 50, 100, 200, 500, and 1000 keV. The dose was converted into specific absorbed fraction (SAF) and the results were compared to the corresponding published MIRD data. On average, there was a good correlation (r (2)>0.99) between the two series of data. However, the GATE/GEANT data were on average -0.16 ± 6.22% lower than the corresponding MIRD data for self-absorption. Self-absorption in the lungs was considerably higher in the MIRD compared to the GATE/GEANT data, for photon energies of 10-20 keV. As for cross-irradiation to other organs, the GATE/GEANT data were on average +1.5 ± 8.1% higher than the MIRD data, for photon energies of 50-1000 keV. For photon energies of 10-30 keV, the relative difference was +7.5 ± 67%. It turned out that the agreement between the GATE/GEANT and the MIRD data depended upon absolute SAF values and photon energy. For 10-30 keV photons, where the absolute SAF values were small, the uncertainty was high and the effect of cross-section prominent, and there was no agreement between the GATE/GEANT results and the MIRD data. However, for photons of 50-1,000 keV, the bias was negligible and the agreement was acceptable.

A study of peroxyoxalate-chemiluminescence of 4,4'-bis{[4,6-bis (2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino}stilbene-2,2'-disulfonic acid-disodium salt as a novel blue fluorescer.

The chemiluminescence arising from the reaction of bis(2,4,6-trichlorophenyl)oxalate (TCPO) with hydrogen peroxide in the presence of brightener 4,4'-bis{[4,6-bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino}stilbene-2,2'-disulfonic acid-disodium salt (Triazinyl) has been studied. The influence of concentration of TCPO, hydrogen peroxide, Triazinyl, base catalysts and temperature on the resulting chemiluminescence was investigated. The kinetic parameters for the peroxyoxalate-chemiluminescence (PO-CL) of Triazinyl were evaluated from computer fitting of the resulting intensity-time plots. The activation energies, E(a), were evaluated from temperature dependence of the corresponding rise and fall rate constants.