Examining Absorbed Doses of Indigenously Developed 177Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer Patients at Baseline and During Course of Peptide Receptor Radioligand Therapy.

Aim: The objective of this study was to estimate the absorbed doses to the normal organs and tumor lesions in metastatic castration-resistant prostate cancer (mCRPC) patients treated with indigenously developed 177Lu-PSMA-617 that could establish optimal treatment protocol with minimum risk to the dose-limiting organs. Furthermore, attempt was also made to compare radiation absorbed doses for normal organs and tumor lesions in subsequent cycles of 177Lu-PSMA-617 peptide receptor radioligand therapy (PRLT) in the same group of patients during the course of treatment. Methods: A total of 30 patients of proven mCRPC were enrolled for this prospective study. These patients received up to 5 cycles of treatment with 177Lu-PSMA-617 PRLT (1 cycle for 13 patients, 2 cycles for 9 patients, 3 cycles for 3 patients, and 5 cycles for 5 patients), at 11-12-week intervals between the two successive therapies. The patients underwent postadministration whole-body scintigraphy at five time points: 0.5 (prevoid), 2, 12, 24, and 72/96 h (postvoid). From time-activity curves generated by drawing regions of interests on the images, number of disintegrations was determined. Tumor masses were estimated from pretherapeutic 68Ga-PSMA-11 positron emission tomography-computed tomography images. Absorbed doses for organs and tumors were calculated using OLINDA 2.0 software. Results: The average activity of 177Lu-PSMA-617 (mean ± SD) administered per patient per cycle was 4.94 ± 0.45 GBq. The mean absorbed organ doses (mean ± SD) from first therapy cycle in Gy/GBq were as follows: kidneys 0.52 ± 0.16, spleen 0.17 ± 0.07, liver 0.08 ± 0.05, salivary glands 0.53 ± 0.30, lacrimal glands 1.45 ± 0.85, nasal mucosa membrane 0.46 ± 0.19, urinary bladder 0.23 ± 0.02, and bone marrow 0.04 ± 0.03. The mean effective dose for whole body from first therapy cycle was 0.05 ± 0.03 Sv/GBq. Among all the normal organs, lacrimal glands received the highest absorbed dose. The median dose for all lesions, bone lesions, lymph nodes, primary site, liver lesion, lung lesion, and soft tissue deposit from first therapy cycle was determined to be 4.17, 4.23, 3.96, 4.36, 10.27, 0.78, and 4.68 Gy/GBq respectively. Absorbed doses received by the normal organs in five consecutive cycles follow three different trends, (a) for kidneys, salivary glands, and nasal mucous membrane, absorbed doses increased from first therapy cycle to second therapy cycle and then slowly decreased in subsequently therapy cycles; (b) for spleen, liver, and lacrimal glands, absorbed doses decreased with the successive therapy cycles; and (c) in case of bone marrow, bladder, and whole body, mean absorbed dose almost remained constant in each therapy cycle. Absorbed doses to the lesions gradually decreased with increase of the number of therapy cycles. Conclusions: The organ and tumor absorbed doses of 177Lu-PSMA-617 in mCRPC patients were found to be comparable to the data reported in the literature. The highest absorbed organ dose was observed in lacrimal glands and being a dose limiting organ, a cumulative activity up to 32.5 GBq (878 mCi) of 177Lu-PSMA-617 in 4-5 therapy cycles appears safe and feasible to achieve full therapeutic window.

Estimation of effective dose and radiation risk in pediatric barium studies procedures.

The objectives of this study are to assess pediatric radiation exposure in certain barium studies and to quantify the organ and effective doses and radiation risk resultant from patients' irradiation. A total of 69 pediatric barium studies for upper and lower gastrointestinal tract. Patients' radiation dose was quantified in terms of Entrance surface air kerma (ESAKs) using exposure parameters and DosCal software. Organ and effective doses (E) were extrapolated using national Radiological Protection Board software (NRPB-R279). The mean ± (SD) and the range of patient doses per procedure were 3.7 ± 0.4 (1.0-13.0)mGy, 7.4 ± 1.7(5.5-8.0)mGy and 1.4 ± 0.9 (0.5-3.6)mGy for barium meal, swallow and enema, respectively. The mean effective doses were 0.3 ± 0.03 (0.08-1.1)mSv, 0.2 ± 1.6 (0.44-0.7)mSv and 0.3 ± 0.9 (0.1-0.8)mSv at the same order. The radiation dose were higher compared to previous studies. Therefore, pediatrics are exposed to avoidable radiation exposure. Certain optimization measures are recommended along with establishing national diagnostic reference level (DRL) to reduce the radiation risk.

Personalized technologist dose audit feedback for reducing patient radiation exposure from CT.

PURPOSE: The aim of this study was to determine whether providing radiologic technologists with audit feedback on doses from CT examinations they conduct and education on dose-reduction strategies reduces patients' radiation exposure. METHODS: This prospective, controlled pilot study was conducted within an integrated health care system from November 2010 to October 2011. Ten technologists at 2 facilities received personalized dose audit reports and education on dose-reduction strategies; 9 technologists at a control facility received no intervention. Radiation exposure was measured by the dose-length product (DLP) from CT scans performed before (n = 1,630) and after (n = 1,499) the intervention and compared using quantile regression. Technologists were surveyed before and after the intervention. RESULTS: For abdominal CT, DLPs decreased by 3% to 12% at intervention facilities but not at the control facility. For brain CT, DLPs significantly decreased by 7% to 12% at one intervention facility; did not change at the second intervention facility, which had the lowest preintervention DLPs; and increased at the control facility. Technologists were more likely to report always thinking about radiation exposure and associated cancer risk and optimizing settings to reduce exposure after the intervention. CONCLUSIONS: Personalized audit feedback and education can change technologists' attitudes about, and awareness of, radiation and can lower patient radiation exposure from CT imaging.

[Computational radiofrequency electromagnetic field dosimetry in evaluation of biological effects].

Given growing computational resources, radiofrequency electromagnetic field dosimetry is becoming more vital in the study of biological effects of non-ionizing electromagnetic radiation. The study analyzes numerical methods which are used in theoretical dosimetry to assess the exposure level and specific absorption rate distribution. The advances of theoretical dosimetry are shown. Advantages and disadvantages of different methods are analyzed in respect to electromagnetic field biological effects. The finite-difference time-domain method was implemented in detail; also evaluated were possible uncertainties of complex biological structure simulation for bioelectromagnetic investigations.

Dose estimates for the local inhabitants from 210Po ingestion via dietary sources at a proposed uranium mining site in India.

PURPOSE: To study the distribution of (210)Po activity in food in Bagjata in East Singhbhum, India. MATERIALS AND METHODS: (210)Po were analyzed in the food samples of plant origin such as cereals, pulses, fruits, vegetables and food of animal origin such fish, chicken, egg, etc., in and around Bagjata uranium mining area as a part of baseline study after acid digestion. The intake and ingestion dose of the radionuclide was estimated. RESULTS: The general range of (210)Po activity in all the dietary components ranged widely from <0.2-36 Bqkg(-1)(fresh). In the food of plant origin, the minimum activity of (210)Po was estimated in vegetables while maximum in pulses. In food of animal origin, the observed minimum activity of (210)Po was in eggs and the maximum observed was in chicken samples. The intake of (210)Po considering all dietary components was found to be 464 Bq.Y(-1) while the ingestion dose was calculated to be 557 µSv.Y(-1), respectively. The estimated doses are reflecting the natural background dose via the route of ingestion, which is much below the 1 mSv limit set in the International Commission on Radiological Protection (ICRP) recommendations. CONCLUSION: The study confirms that current levels of (210)Po do not pose a significant radiological risk to the local inhabitants.

Annual committed effective dose from olive oil (due to 238U, 232Th, and 222Rn) estimated for members of the Moroccan public from ingestion and skin application.

Olive oil is traditionally refined and widely consumed by Moroccan rural populations. Uranium (238U), thorium (232Th), radon (222Rn), and thoron (220Rn) contents were measured in various locally produced olive oil samples collected in rural areas of Morocco. These radionuclides were also measured inside various bottled virgin olive oils consumed by the Moroccan populations. CR-39 and LR-115 type II solid state nuclear track detectors (SSNTDs) were used. Annual committed effective doses due to 238U, 232Th, and 222Rn from the ingestion of olive oil by the members of the general public were determined. The maximum total committed effective dose due to 238U, 232Th, and 222Rn from the ingestion of olive oil by adult members of Moroccan rural populations was found equal to 5.9 µSv y-1. The influence of pollution due to building material dusts and phosphates on the radiation dose to workers from the ingestion of olive oil was investigated, and it was found that the maximum total committed effective dose due to 238U, 232Th, and 222Rn was on the order of 0.22 mSy y-1. Committed effective doses to skin due to 238U, 232Th, and 222Rn from the application of olive oil masks by rural women were evaluated. The maximum total committed effective dose to skin due to 238U, 232Th, and 222Rn was found equal to 0.07 mSy y-1 cm-2.

Radiation hardness of the storage phosphor europium doped potassium chloride for radiation therapy dosimetry.

PURPOSE: An important property of a reusable dosimeter is its radiation hardness, that is, its ability to retain its dosimetric merits after irradiation. The radiation hardness of europium doped potassium chloride (KC1:Eu2+), a storage phosphor material recently proposed for radiation therapy dosimetry, is examined in this study. METHODS: Pellet-style KCl:Eu2+ dosimeters, 6 mm in diameter, and 1 mm thick, were fabricated in-house for this study. The pellets were exposed by a 6 MV photon beam or in a high dose rate 137Cs irradiator. Macroscopic properties, such as radiation sensitivity, dose response linearity, and signal stability, were studied with a laboratory photostimulated luminescence (PSL) readout system. Since phosphor performance is related to the state of the storage centers and the activator, Eu2+, in the host lattice, spectroscopic and temporal measurements were carried out in order to explore radiation-induced changes at the microscopic level. RESULTS: KCl:Eu2+ dosimeters retained approximately 90% of their initial signal strength after a 5000 Gy dose history. Dose response was initially supralinear over the dose range of 100-700 cGy but became linear after 60 Gy. Linearity did not change significantly in the 0-5000 Gy dose history spanned in this study. Annealing high dose history chips resulted in a return of supralinearity and a recovery of sensitivity. There were no significant changes in the PSL stimulation spectra, PSL emission spectra, photoluminescence spectra, or luminescence lifetime, indicating that the PSL signal process remains intact after irradiation but at a reduced efficiency due to reparable radiation-induced perturbations in the crystal lattice. CONCLUSIONS: Systematic studies of KCl:Eu2+ material are important for understanding how the material can be optimized for radiation therapy dosimetry purposes. The data presented here indicate that KCl:Eu2+ exhibits strong radiation hardness and lends support for further investigations of this novel material.

Does the amount of tagged stool and fluid significantly affect the radiation exposure in low-dose CT colonography performed with an automatic exposure control?

OBJECTIVE: To determine whether the amount of tagged stool and fluid significantly affects the radiation exposure in low-dose screening CT colonography performed with an automatic tube-current modulation technique. METHODS: The study included 311 patients. The tagging agent was barium (n = 271) or iodine (n = 40). Correlation was measured between mean volume CT dose index (CTDI (vol)) and the estimated x-ray attenuation of the tagged stool and fluid (ATT). Multiple linear regression analyses were performed to determine the effect of ATT on CTDI (vol ) and the effect of ATT on image noise while adjusting for other variables including abdominal circumference. RESULTS: CTDI (vol) varied from 0.88 to 2.54 mGy. There was no significant correlation between CTDI (vol) and ATT (p = 0.61). ATT did not significantly affect CTDI (vol) (p = 0.93), while abdominal circumference was the only factor significantly affecting CTDI (vol) (p < 0.001). Image noise ranged from 59.5 to 64.1 HU. The p value for the regression model explaining the noise was 0.38. CONCLUSION: The amount of stool and fluid tagging does not significantly affect radiation exposure.

Dosimetry parameters of the IRH10 192Ir high dose rate brachytherapy source.

The dosimetry parameters of the IRH10 (192)Ir high dose rate brachytherapy source were obtained from the dose calculation formalism recommended in the AAPM Task Group No. 43 report using the Monte Carlo code PENELOPE. The absorbed doses to water and air originating from the photons of the IRH10 (192)Ir brachytherapy source were calculated by the collision kerma approximation. The dose rate constant was evaluated to be (1.110 +/- 0.011) cGy/h U(-1). The dose rate per unit air kerma strength around the (192)Ir IRH10 brachytherapy source and the anisotropy function were given in tables and figures.

Evaluation of all dose components in the LVR-15 reactor epithermal neutron beam using Fricke gel dosimeter layers.

Fricke gel dosimeters in the form of layers are suitable to reconstruct bidimensional distributions of the absorbed dose; in accordance with their chemical composition and applying suitably developed algorithms, they can provide dose images of the different radiation components in a BNCT field. After the description of the applied method, this work presents the results obtained at the epithermal column of the BNCT facility at the NRI in Rez (CZ). The measured dose distributions are shown in comparison with data taken by means of other dosimeters thermoluminescence dosimeters (TLDs) and with calculations carried out with the Monte Carlo code MCNP5. The agreement with the results obtained by means of the different techniques is satisfying.

Characterization of a fiber-coupled Al2O3:C luminescence dosimetry system for online in vivo dose verification during 192Ir brachytherapy.

A prototype of a new dose-verification system has been developed to facilitate prevention and identification of dose delivery errors in remotely afterloaded brachytherapy. The system allows for automatic online in vivo dosimetry directly in the tumor region using small passive detector probes that fit into applicators such as standard needles or catheters. The system measures the absorbed dose rate (0.1 s time resolution) and total absorbed dose on the basis of radioluminescence (RL) and optically stimulated luminescence (OSL) from aluminum oxide crystals attached to optical fiber cables (1 mm outer diameter). The system was tested in the range from 0 to 4 Gy using a solid-water phantom, a Varian GammaMed Plus 192Ir PDR afterloader, and dosimetry probes inserted into stainless-steel brachytherapy needles. The calibrated system was found to be linear in the tested dose range. The reproducibility (one standard deviation) for RL and OSL measurements was 1.3%. The measured depth-dose profiles agreed well with the theoretical expectations computed with the EGSNRC Monte Carlo code, suggesting that the energy dependence for the dosimeter probes (relative to water) is less than 6% for source-to-probe distances in the range of 2-50 mm. Under certain conditions, the RL signal could be greatly disturbed by the so-called stem signal (i.e., unwanted light generated in the fiber cable upon irradiation). The OSL signal is not subject to this source of error. The tested system appears to be adequate for in vivo brachytherapy dosimetry.

Clinic based transfer of the N(D,W)(60Co) calibration coefficient using a linear accelerator.

Ionization chambers used for reference dosimetry require a local secondary standard ionization chamber with a 60Co absorbed dose to water calibration coefficient N(D,W)(60Co) traceable to a national primary standards dosimetry laboratory or an accredited secondary dosimetry calibration laboratory. Clinic based (in-house) transfer of this coefficient to tertiary reference ionization chambers has traditionally been accomplished with chamber cross calibration in water using a 60Co beam; however, access to 60Co teletherapy machines has become increasingly limited for clinic based physicists. In this work, the accuracy of alternative methods of transferring the N(D,W)(60Co) calibration coefficient using 6 and 18 MV photon beams from a linear accelerator in lieu of 60Co has been investigated for five different setups and four commonly used chamber types.

LVR-15 reactor epithermal neutron beam parameters--results of measurements.

The epithermal neutron beam of the LVR-15 reactor provides the appropriate conditions for varied BNCT activity. The principal parameters have been frequently determined. The following detectors have been used for the measurement: set of activation monitors of different nuclides irradiated in free beam and in the water phantom, Si semiconductor detector with (6)LiF converter, twin ionization chambers, thermoluminescence dosimeters, gel dosimeters used for imaging of separate part of dose, neutron spectrometer of Bonner type. Obtained results of measured parameters are presented in the paper.

Modelling optical scattering artefacts for varying pathlength in a gel dosimeter phantom.

A gelatin phantom containing an optically scattering funnel-shaped region of elevated optical density (OD) was used to examine light-scattering-induced artefacts in a cone-beam optical CT scanner used for gel dosimetry. To simulate polymer gel dosimeters, the opacity was introduced by adding a colloidal scatterer to the gelatin. Scatter results in an underestimate of OD (hence dose). In line profiles of OD taken from 3D reconstructions of the funnel, those profiles with a long pathlength through high OD regions exhibited a 'dishing' (or 'cupping') artefact, while those of short pathlength exhibited the opposite effect-'doming'. These phenomena are accounted for by a model that includes the effect of stray, scattered light.

Moderated 252Cf neutron energy spectra in brain tissue and calculated boron neutron capture dose.

While there is significant clinical experience using both low- and high-dose (252)Cf brachytherapy, combination therapy using (10)B for neutron capture therapy-enhanced (252)Cf brachytherapy has not been performed. Monte Carlo calculations were performed in a brain phantom (ICRU 44 brain tissue) to evaluate the dose enhancement predicted for a range of (10)B concentrations over a range of distances from a clinical (252)Cf source. These results were compared to experimental measurements and calculations published in the literature. For (10)B concentrations

In-phantom imaging of all dose components in boron neutron capture therapy by means of gel dosimeters.

The experimental method for in-phantom imaging and profiling the absorbed dose in neutron capture therapy has been improved. The method separates the contributions of the various secondary radiation components and is based on suitably designed gel dosimeters in the form of layers. The discrimination of the dose components is achieved by means of pixel-to-pixel manipulations of images obtained with gel dosimeters having different isotopic composition. Large dose images are obtainable with this method, because the layer geometry of dosimeters avoids sensible variation of neutron transport due to the isotopic composition of gel. Operation modalities aimed at attaining more reliable results have been studied. Some results, together with the results of punctual measurements performed with conventional dosimeters and with MC calculations, are here reported.

Biologic monitoring for urinary uranium in gulf war I veterans.

Biologic monitoring for total uranium in urine of Gulf War I veterans concerned about past exposure to depleted uranium (DU) has been offered by the Departments of Veterans Affairs and Defense since the late 1990's. DU, a component of U.S. munitions and tank armor, was first used during that conflict. Two hundred and twenty-seven veterans submitted samples for analysis from January 2000 through December 2002, which included a 24-h urine sample for determination of total urinary uranium concentration and completed questionnaires describing their wartime exposure experiences. Thirty questionnaire items characterizing DU exposure opportunities were collapsed into 19 exposure categories. Urine uranium (U) results were stratified into low and high uranium groups with 0.05 microg U g creatinine as the cut point. Exposure scenarios in the high and low uranium groups were similar in frequency and type with only the presence of retained shrapnel being predictive of a high urine uranium value, as found in the first phase of this surveillance of 169 veterans performed prior to 2000. Twenty-two veterans exhibited U levels in the high range. Isotopic analysis, available for 21 of these 22, revealed that all but three of these samples contained natural and not depleted uranium. These three participants had retained DU shrapnel as a result of their past injuries. Thus, even with an enlarged cohort, elevated urine uranium values in the absence of retained DU fragments are unlikely. The utility of isotopic analysis to more fully characterize uranium biomonitoring results is also demonstrated.

The use of biologically based cancer risk models in radiation epidemiology.

Biologically based risk projection models for radiation carcinogenesis seek to describe the fundamental biological processes involved in neoplastic transformation of somatic cells into malignant cancer cells. A validated biologically based model, whose parameters have a direct biological interpretation, can also be used to extrapolate cancer risks to different exposure conditions with some confidence. In this article biologically based models for radiation carcinogenesis, including the two-stage clonal expansion (TSCE) model and its extensions, are reviewed. The biological and mathematical bases for such models are described, and the implications of key model parameters for cancer risk assessment examined. Specific applications of versions of the TSCE model to important epidemiological datasets are discussed, including the Colorado uranium miners' cohort; a cohort of Chinese tin miners; the lifespan cohort of atomic bomb survivors in Hiroshima and Nagasaki; and a cohort of over 200,000 workers included in the National Dose Registry (NDR) of Canada.

Uranium content in phosphate fertilizers commercially produced in Brazil.

This work presents the results of the determination of uranium concentration in the most commonly used phosphate fertilizers employed in Brazilian agricultural land. The technique employed was the nuclear fission track registration in plastic foils of Makrofol KG (dry method), together with a discharge chamber system for track counting. Phosphate fertilizer samples and uranium standards were irradiated together with thermal neutrons in the 2 MW IEA-R1 research reactor of IPEN/SP. The uranium concentration in Brazilian phosphate fertilizers ranging from 5.17 to 54.3 ppm is in good agreement with the results reported in the literature for similar fertilizers produced in other countries.

Comparison of high-energy photon and electron dosimetry for various dosimetry protocols.

The American Association of Physicists in Medicine Task Group 51 (TG-51) and the International Atomic Energy Agency (IAEA) published a new high-energy photon and electron dosimetry protocol, in 1999 and 2000, respectively. These protocols are based on the use of an ion chamber having an absorbed-dose to water calibration factor with a 60Co beam. These are different from the predecessors, the TG-21 and IAEA TRS-277 protocols, which require a 60Co exposure or air-kerma calibration factor. The purpose of this work is to present the dose comparison between various dosimetry protocols and the AAPM TG-51 protocol for clinical reference dosimetry of high-energy photon and electron beams. The absorbed-dose to water calculated according to the Japanese Association of Radiological Physics (JARP), International Atomic Energy Agency Technical Report Series No. 277 (IAEA TRS-277) and No. 398 (IAEA TRS-398) protocols is compared to that calculated using the TG-51 protocol. For various Farmer-type chambers in photon beams, TG-51 is found to predict 0.6-2.1% higher dose than JARP. Similarly, TG-51 is found to be higher by 0.7-1.7% than TRS-277. For electron beams TG-51 is higher than JARP by 1.5-3.8% and TRS-277 by 0.2-1.9%. The reasons for these differences are presented in terms of the cavity-gas calibration factor, Ngas, and a dose conversion factor, Fw, which converts the absorbed-dose to air in the chamber to the absorbed-dose to water. The ratio of cavity-gas calibration factors based on absorbed-dose to water calibration factors, N60Co(D,w), in TG-51 and cavity-gas calibration factors which are equivalent to absorbed-dose to air chamber factors, N(D,air), based on the IAEA TRS-381 protocol is 1.008 on average. However, the estimated uncertainty of the ratio between the two cavity-gas calibration factors is 0.9% (1 s.d.) and consequently, the observed difference of 0.8% is not significant. The absorbed-dose to water and exposure or air-kerma calibration factors are based on standards traceable to the National Institute of Standards and Technology (NIST). In contrast, the absorbed-dose to water determined with TRS-398 is in good agreement with TG-51 within about 0.5% for photon and electron beams.