Radiation absorbed dose to the embryo/fetus from radiopharmaceuticals

Radiation protection practice requires the knowledge of estimated absorbed radiation doses to aid in the understanding of the potential detriment of various exposures. In nuclear medicine, the radiation doses to the internal organs of the subject are commonly calculated using the MIRD methods and equations. The absorbed dose to the embryo or fetus has long been an area of concern. The recent release of the pregnant female phantom series, and its incorporation into the MIRDOSE 3 computer software, has made possible the estimation of absorbed doses from radionuclides in the body to the fetus in early pregnancy and at 3, 6, and 9 mo gestation. A survey of several major medical institutions was made to determine the radiopharmaceuticals which might be given, whether intentionally or not, to women of childbearing years. Biokinetic data for these radiopharmaceuticals were gathered from various documents and other resources, and the absorbed doses to the embryo and fetus at these different stages of gestation from radiations originating within the mother's organs were estimated. In addition, information about activity distributed within the placenta and fetus was included where quantitative data were available. These absorbed dose estimates can be used to evaluate the risk associated with the use of different radiopharmaceuticals so that a more informed evaluation of the risks and benefits of the different procedures may be made. Further research is needed into the mechanisms and quantitative aspects of the placental transfer of many radiopharmaceuticals.     

Induction of apoptotic cell death in human leukemic cell line, HL-60, by extremely low frequency electric magnetic fields: analysis of the possible mechanisms in vitro

An anthropomorphic Rando phantom was used to compare radiation doses sustained during helical and conventional axial CT of the pelvis. The values obtained with the Rando phantom were validated against cadaveric phantoms, and show good agreement. For the authors' particular CT unit, helical scanning was found to deliver a lower radiation dose than conventional axial scanning. This was most prominent at 1.0-s tube rotation times (average dose ratio 1.24). For realistic scanning parameters and exposure factors, the ratio of radiation dose to pelvic organs can be expected to lie in the range of 40-100 mGy. The whole-body effective dose (ED) depends on selection of scanning parameters and patients anatomy. In a favourable case scenario, the ED for CT scanning of the pelvis in a male can be expected to be between 10 and 20 mSv if the scrotum is not included in the radiation field, while the ED in a female will be approximately 20 mSv. An examination of scatter radiation fall-off curves from a single slice shows that the spread of scatter radiation is only marginally affected by slice thickness. A total of 10-12 cm of human soft tissue acts as a good barrier against internal scattered radiation. The use of such scatter fall-off curves, together with manufacturers' dosimetry specifications, allows a fast estimate of absorbed dose.     

Conversion of ionization measurements to radiation absorbed dose in non-water density material

The radiation absorbed dose to non-water equivalent materials of interest in radiotherapy is the dose to lung and the dose to bone. The measurement and calculation of dose to the lung has been of great interest and much effort has gone into the development of accurate lung dose calculation methods. The radiation absorbed dose to the bone is usually not calculated and most absorbed dose calculations have been done without correcting for the presence of bone. For the lower megavoltage photon beams this may be appropriate, however, as the energy of the photon beam increases, the region of electronic disequilibrium becomes larger and pair production which depends on the atomic number of the material becomes significant. Therefore the bone will produce greater perturbations of the dose distribution. The dose to lung-equivalent material is uniquely obtained from ionization measurements. However, in bone-equivalent materials two different calculations of absorbed dose are possible: the absorbed dose to soft tissue plastic (polystyrene) within bone-equivalent material and the dose to the bone-equivalent material itself. Both can be calculated from ionization measurements in phantoms. These two calculations result in significantly different doses in a heterogeneous phantom composed of polystyrene and aluminium (a bone substitute). The dose to a thin slab of polystyrene in aluminium is much higher than the dose to the aluminium itself at the same depth in the aluminium. Monte Carlo calculations confirm that the calculation of dose to polystyrene in aluminium can be accurately carried out using existing dosimetry protocols. However, the conversion of ionization measurements to absorbed dose to high atomic number materials cannot be accurately carried out with existing protocols and appropriate conversion factors need to be determined.     

Studies on the desamidation of bovine collagen

A variable air-volume, parallel-plate extrapolation chamber forming an integral part of a Solid Water phantom was built to determine the absorbed dose in Solid Water directly. The sensitive air-volume of the extrapolation chamber is controlled through the movement of the chamber piston by means of a micrometer mounted to the phantom body. The relative displacement of the piston is monitored by a calibrated mechanical distance travel indicator with a precision on the order of 0.002 mm. Irradiations were carried out with cobalt-60 gamma rays, x-ray beams ranging from 4 to 18 MV, and electron beams between 6 and 22 MeV. The absorbed dose at a given depth in Solid Water is proportional to the ionization gradient measured in the Bragg-Gray cavity region with an extrapolation chamber embedded in the Solid Water phantom. The discrepancies between the doses determined in Solid Water with our uncalibrated extrapolation chamber and doses obtained with a calibrated standard thimble ionization chamber are at most 1% for photon and electron beams at all megavoltage clinical energies. Uncalibrated extrapolation chamber thus offer a simple and practical alternative to other techniques used in output measurements of megavoltage photon and electron machines.     

Estimation of organ cumulated activities and absorbed doses on intakes of several 11C labelled radiopharmaceuticals from external measurement with thermoluminescent dosimeters

We have developed a method for obtaining the cumulated activities in organs from radionuclides, which are injected into the patient in nuclear medicine procedures, by external exposure measurement with thermoluminescent dosimeters (TLDs) which are attached to the patient's body surface close to source organs to obtain information on body-surface doses. As the surface dose is connected to the cumulated activities in source organs through radiation transmission in the human body which can be estimated with the aid of a mathematical phantom, the organ cumulated activities can be obtained by the inverse transform method. The accuracy of this method was investigated by using a water phantom in which several gamma-ray volume sources of known activity were placed to simulate source organs. We then estimated by external measurements the organ cumulated activities and absorbed doses in subjects to whom the radiopharmaceuticals 11C-labelled Doxepin, 11C-labelled YM09151-2 and 11C-labelled Benzotropin were administered in clinical nuclear medicine procedures. The cumulated activities in the brain obtained with TLDs for Doxepin and YM09151-2 are 63.6 +/- 6.2 and 32.1 +/- 12.0 kBq h MBq-1 respectively, which are compared with the respective values of 33.3 +/- 9.9 and 23.9 +/- 6.2 kBq h MBq-1 with direct PET (positron emission tomography) measurements. The agreement between the two methods is within a factor of two. The effective doses of Doxepin, YM09151-2 and Benzotropin are determined as 6.92 x 10(-3), 7.08 x 10(-3) and 7.65 x 10(-3) mSv MBq-1 respectively with the TLD method. This method has great advantages, in that cumulated activities in several organs can be obtained easily with a single procedure, and the measurements of body surface doses are performed simultaneously with the nuclear medicine procedure, as TLDs are too small to interfere with other medical measurements.     

Dynamics of radiation environment of space station "Mir" by the "DOZA-A1" readings

One of the serious disadvantages of the U.S. (AP-8 and AE-8) and Russian trapped radiation models is the lack of data concerning the dynamics of trapped particles fluences within a time interval shorter than the solar cycle. The available models are capable to predict the energy spectra of trapped particles only for periods in the vicinity of the solar minimum or maximum. The current models are also lacking data about the angular distribution of trapped particles. Meanwhile, these facts are important in conjunction with the problems of radiation safety of space crews. DOZA-A1 incorporating 7 semiconductor detector with a dose sensitivity of 2.4. 10(-4) muGy/pulse and a temporal resolution of 15 seconds, and a reading and charging unit were delivered to MIR in September, 1995; the experiment began in January, 1996. Measurements were made in three locations of the basal module. The articles deals with the analysis and comparison of experimental data with results of other dosimetric determinations and predictions of the trapped radiation models.     

Validation of serum transthyretin (prealbumin) as a nutritional parameter in hemodialysis patients

Discoloring of glass due to ionizing radiation depends on the absorbed dose. The radiation-induced light attenuation in optical fibers may be used as a measure of the dose. In high-energy photon beams (6 MV X rays), a lead-doped silica fiber can be calibrated. A dosimeter based on an optical fiber was developed for applications in radiation therapy. The diameter of the mounted fiber is 0.25 mm, whereas the length depends on the sensitivity required. To demonstrate the applicability, a customized fiber device was used to determine scattered radiation close to the lens of the eye. Measurements were compared with TLDs (LiF) in an anthropomorphic phantom. The comparison with TLD measurements shows good agreement. In contrast to TLD, optical fibers provide immediate dose values, and the readout procedure is much easier. Owing to its small size and diameter, interesting invasive dose measurements are feasible.     

TLD array for precise dose measurements in stereotactic radiation techniques

We developed a new TLD array for precise dose measurement and verification of the spatial dose distribution in small radiation targets. It consists of a hemicylindrical, tissue-equivalent rod made of polystyrene with 17 parallel moulds for an exact positioning of each TLD. The spatial resolution of the TLD array was evaluated using the Leskell spherical phantom. Dose planning was performed with KULA 4.4 under stereotactic conditions on axial CT images. In the Leksell gamma unit the TLD array was irradiated with a maximal dose of 10 Gy with an unplugged 14 mm collimator. The doses delivered to the TLDs were rechecked by diode detector and film dosimetry and compared to the computer-generated dose profile. We found excellent agreement of our measured values, even at the critical penumbra decline. For the 14 mm and 18 mm collimator and for the 11 mm collimator combination we compared the measured and calculated data at full width at half maximum. This TLD array may be useful for phantom or tissue model studies on the spatial dose distribution in confined radiation targets as used in stereotactic radiotherapy.     

Microdosimetric specification of the radiation quality of a d(48.5)+Be fast neutron therapy beam produced by a superconducting cyclotron

The proportional counter microdosimetric technique has been employed to quantify variations in the quality of a d(48.5)+Be fast neutron beam passing through a homogeneous water phantom. Single event spectra have been measured as a function of spatial location in the water phantom and field size. The measured spectra have been separated into component spectra corresponding to the gamma, recoil proton and alpha plus heavy recoil ion contribution to the total absorbed dose. The total absorbed dose normalized to the "monitor units" used in daily clinical use has been calculated from the measured spectra and compared to the data measured with calibrated ion chambers. The present measurements agree with the ion chamber data to within 5%. The RBE of the neutron beam is assumed to be proportional to the microdosimetric parameter y* for the dose ranges pertinent to fractionated neutron therapy. The relative variations in y*, assumed to be representative of variations in the RBE are mapped as a function of field size and spatial location in the phantom. A variation in the RBE of about 4% for points within and 8% for points outside a 10 cm x 10 cm field is observed. The variations in the RBE within the beam are caused by an increase in the gamma component with depth. An increase in the RBE of about 4% is observed with increasing field size which is attributed to a change in the neutron spectrum. Compared to the uncertainties in the prescribed dose, associated with uncertainties in the clinically used RBE, variation in the RBE between various tissues, and other dosimetric uncertainties caused by factors such as patient inhomogeneities, patient setup errors, patient motion, etc., the measured spatial RBE variations are not considered significant enough to be incorporated into the treatment planning scheme.     

A CT assisted method for absolute quantitation of internal radioactivity

A method is described for the determination of radioactivity (microCi or MBq) at an organ site within an object or patient. Using both anatomic image data (CT or MRI scans) and planar gamma camera images, activity at depth is determined using a matrix inversion method based on least squares. The result of the inversion analysis was the unknown set of n linear (uniform) activity densities representative of each organ within the phantom or patient. The problem was overdetermined since the number of unknown activity densities (microCi/cm) was much less than the number of analysis points (N) within the nuclear image. This method, defined as the CT assisted matrix inversion (CAMI) technique, was accurate to within 15% for a three "organ" plastic phantom, wherein the organs were right circular cylinders having activities of 74 to 508 microCi (or 2.74 MBq to 18.8 MBq). This accuracy included image quantitation effects, particularly assumptions concerning attenuation correction. The average absolute percent error of the estimated activity in four distinct radioactive volumes in the phantom was 9.8%. It was found that the background activity within the phantom was estimated to be too high if sampling regions near strong sources were used in the analysis (scatter effect). This was minimized by going at least 2 cm away from such sources. By applying the method to a monoclonal antibody clinical study, activities within the patient's major organs such as liver, spleen, and kidney could be estimated, even in cases where the organ could not be visualized. Here, the CAMI algorithm gave internally consistent results for the patient's left and right lung linear activity concentrations. The CAMI technique resolves the problem of tissue superimposition using depth information from 3-D CT and is applicable in cases where a number of organs overlap in the gamma camera image. Thus, the method should be generally useful to nuclear image quantitation and the estimation of absorbed radiation doses in patients. One particular application is the estimation of radiation doses in radioimmunotherapy (RIT).     

Radiation dose and image quality in spiral computed tomography: multicentre evaluation at six institutions

The purpose of this study was to evaluate the correlation of radiation dose with image quality in spiral CT. Seven clinical protocols were measured in six different radiological departments provided with four different types of high specification spiral CT scanners. Central and surface absorbed doses were measured in acrylic. The practical CT dose index (PCTDI) was calculated for seven clinical examination protocols and one standardized protocol using identical parameters on four different spiral CT scanners with a dedicated ionization chamber inserted into PMMA phantoms. For low contrast measurements, a cylindrical three-dimensional (3D) phantom (different sized spheres of defined contrast) was used. Image noise was measured with a cylindrical water phantom and high contrast resolution with a Perspex hole phantom. Image quality phantoms were scanned using the parameters of the clinical protocols. Images were randomized, blinded and read by six radiologists (one from each institution). PCTDI values for four different scanners varied up to a factor between 1.5 (centre) and 2.2 (surface) for the standardized protocol. A greater degree of variation was observed for seven clinical examination protocols of the six radiological departments. For example, PCTDI varied up to a factor between 1.7 (cerebrum protocol) and 8.3 (abdomen paediatric protocol). Low contrast resolution correlates closely with dose. An improvement in detection from 8 mm to 4 mm sized spheres needs approximately a ten-fold increase in dose. Noise shows a moderate correlation with PCTDI. High contrast resolution of clinical protocols is independent of PCTDI within a certain range. Differences in modern CT scanner technology seem to be of less importance for radiation exposure than selection of protocol parameters in different radiological institutes. Future discussion on guidelines regarding optimal (patient adapted) tube current for clinical protocols is desirable.     

Novel metallo beta-lactamase mediated by a Shigella flexneri plasmid

DNA damage by UV radiation plays an essential role in skin cancer induction. We report that even sub-erythemal doses of solar simulating radiation, are capable of inducing substantial nuclear damage, namely pyrimidine dimers and p53 induction in human skin in situ. The quantity and distribution of p53 induced in human skin by UV radiation depended highly on the waveband and dose of UV used. Solar simulating radiation induced very high levels of p53 throughout all layers in epidermal keratinocytes 24 hr following an erythemal dose (230+/-15.9/1000 cells), and the induction followed a dose response. Following UVA I + II and UVA I radiations, p53 expression was approximately half of that seen with equivalent biological doses of solar simulating radiation (63.5+/-28.5 and 103+/-15.9, respectively). Expression of p53 was seen in basal cell keratinocytes at lower doses of UVA, but all layers of the epidermis were affected at higher doses. Pyrimidine dimer induction, however, was seen to be the same for equivalent biological doses of UVA I, UVA I + II and solar simulating radiations, which coincides with previous findings that pyrimidine dimers initiate the erythemal response and are implicated in skin carcinogenesis. When equivalent biological doses of pure UVA are used with no UVB contamination, significant nuclear alterations occur in human skin in situ, which can approach those seen with UVB radiation. Our results suggest that DNA damage assessed in vivo by immunohistochemistry could provide a very sensitive endpoint for determining the efficacy of protective measures, such as sunscreens or protective clothing, against both UVB- and UVA-induced damage in human skin.     

A comparative study of dosimetric properties of Plastic Water and Solid Water in brachytherapy applications

In this study the dosimetric properties of Plastic Water and Solid Water phantom materials are evaluated using Monte Carlo photon transport simulations. In particular, their water-equivalence with respect to absorption and attenuation of photons in the brachytherapy energy range are examined. For the given chemical compositions of the materials, the linear attenuation coefficients were calculated for photons of 1 keV-2 MeV. Moreover, absorbed doses to water in each phantom material were calculated at distances of 0.5-12.0 cm from point sources of 20 keV to 60Co gamma rays. These results show that at low photon energies (below 100 keV), there are substantial differences (up to a factor of 5) between the absorbed dose in Plastic Water and that in liquid water. The differences decrease as photon energy increases, and they become insignificant at 60Co gamma rays, as claimed by the manufacturer. In contrast, calculations show that the difference in absorbed dose in Solid Water from that in liquid water, over the entire range of photon energies employed in this study, is less than 25%. The results of this study demonstrate the necessity of careful dosimetric evaluation of a new phantom material, before its clinical application, particularly in energy ranges outside those referred to by the manufacturer.     

Changes in RBE of 14-MeV (d + T) neutrons for V79 cells irradiated in air and in a phantom: is RBE enhanced near the surface?

PURPOSE: The relative biological effectiveness (RBE) for inactivation of V79 cells was determined as function of dose at the Heidelberg 14-MeV (d + T) neutron therapy facility after irradiation with single doses in air and at different depths in a therapy phantom. Furthermore, to assess the reproducibility of RBE determinations in different experiments we examined the relationship between the interexperimental variation in radiosensitivity towards neutrons with that towards low LET 60Co photons. METHODS: Clonogenic survival of V79 cells was determined using the colony formation assay. The cells were irradiated in suspension in small volumes (1.2 ml) free in air or at defined positions in the perspex phantom. Neutron doses were in the range, Dt = 0.5-4 Gy. 60Co photons were used as reference radiation. RESULTS: The radiosensitivity towards neutrons varied considerably less between individual experiments than that towards photons and also less than RBE. However, the mean sensitivity of different series was relatively constant. RBE increased with decreasing dose per fraction from RBE = 2.3 at 4 Gy to RBE = 3.1 at 0.5 Gy. No significant difference in RBE could be detected between irradiation at 1.6 cm and 9.4 cm depth in the phantom. However, an approximately 20% higher RBE was found for irradiation free in air compared with inside the phantom. Combining the two effects, irradiation with 0.5 Gy free in air yielded an approximately 40% higher RBE than a dose of 2 Gy inside the phantom. CONCLUSION: The measured values of RBE as function of dose per fraction within the phantom is consistent with the energy of the neutron beam. The increased RBE free in air, however, is greater than expected from microdosimetric parameters of the beam and may be due to slow recoil protons produced by interaction of multiply scattered neutrons or to an increased contribution of alpha particles from C(n, alpha) reactions near the surface. An enhanced RBE in subcutaneous layers of skin combined with an increase in RBE at low doses per fraction outside the target volume could potentially have significant consequences for normal tissue reactions in radiotherapy patients treated with fast neutrons.     

Solar urticaria enhanced through clothing

Solar urticaria is characterized by itching, erythema and wheeling immediately after exposure to radiation in the ultraviolet (UVB, UVA) and visible spectra. Although its exact mechanism remains unknown, evidence supports an immunologic pathogenesis. We describe an unusual patient with solar urticaria who had more severe involvement in skin irradiated with UVA light through white clothing. We propose that optical whiteners in clothing and detergents had absorbed UVA radiation, transforming it into visible light, which was responsible for the urticarial response.     

A model of the prostate gland for use in internal dosimetry

Several radionuclides or radiolabeled pharmaceuticals may be taken up by the prostate gland. METHODS: A model of the prostate gland has been developed and implemented in the adult male mathematical phantom within software which calculates absorbed fractions of energy from activity in source regions within the phantom. RESULTS: Specific absorbed fractions are reported for all target regions within the phantom for 12 discrete source energies from 0.01 to 4.0 MeV. S-values for all target regions for six radionuclides are also reported. CONCLUSIONS: This work provides another organ useful for internal dose calculations within the 70-kg phantom.     

Dosimetry of rhenium-186-labeled monoclonal antibodies: methods, prediction from technetium-99m-labeled antibodies and results of phase I trials

Rhenium-186 is a beta-emitting radionuclide that has been studied for applications in radioimmunotherapy. Its 137 keV gamma photon is ideal for imaging the biodistribution of the immunoconjugates and for obtaining gamma camera data for estimation of dosimetry. Methods used for determining radiation absorbed dose are described. We have estimated absorbed dose to normal organs and tumors following administration of two different 186Re-labeled immunoconjugates, intact NR-LU-10 antibody and the F(ab')2 fragment of NR-CO-02. Tumor dose estimates in 46 patients varied over a wide range, 0.4-18.6 rads/mCi, but were similar in both studies. Accuracy of activity estimates in superficial tumors was confirmed by biopsy. Prediction of 186Re dosimetry from a prior 99mTc imaging study using a tracer dose of antibody was attempted in the NR-CO-02 (Fab')2 study. Although 99mTc was an accurate predictor of tumor localization and the mean predicted and observed radiation absorbed doses to normal organs compared favorably, 186Re dosimetry could not be reliably predicted in individual patients. The methods described nevertheless provide adequate estimates of 186Re dosimetry to tumor and normal organs.     

Solar radiation and melanomas--is there any doubt about the connection?

Arguments for and against there being a connection between exposure to solar radiation and cutaneous, malignant melanoma are reviewed. Recent experiments with animals and epidemiological observations provide relatively strong arguments that solar radiation causes cutaneous, malignant melanoma. Furthermore, epidemiological data from Norway and Australia support the assumption that UVA-radiation plays a significant role in melanoma induction; this is in agreement with data from experiments with Xiphophorus and Monodelphis domestica. A new hypothesis for melanoma induction is presented: Radiation absorbed by melanin in melanocytes generates free radicals that may activate the carcinogenic process. Radicals produced by light absorption in melanin in the upper layers of the epidermis are not able to diffuse as far down as to the melanocytes. Thus, this melanin may be protective, while that in the melanocytes may be a photocarcinogen. Findings that support this hypothesis are discussed.     

A phantom for diffusion-weighted imaging of acute stroke

A tissue phantom for diffusion-weighted imaging was developed, basing its contrast between two compartments on different apparent diffusion coefficients, without contrast due to T2 relaxation and proton density. These contrast properties of the phantom simulate the situation found in normal gray matter and areas of acute ischemia. A possible application of the phantom was demonstrated for the investigation of the accuracy of volume measurements based on diffusion-weighted images.     

Radiation dose in critical organs due to non-coplanar irradiation of the hypophysis

BACKGROUND: In order to estimate the somatic and genetic risk associated with a non-coplanar linac-based radiation technique of the pituitary gland, systematic secondary-dose measurements in a phantom and sample measurements of the dose near critical organs of patients were performed. PATIENTS AND METHODS: For measurements of the dose outside the primary radiation field an acrylic-PVC phantom was used which was irradiated with a single field (4 x 4 cm2). Eight patients with pituitary tumors were treated isocentrically with a combination of sagittal and transverse rotational arcs. To measure the dose in critical organs. LiF thermoluminescence dosimeters (TLD) in chip form were placed onto 1 eyelid, the skin over the thyroid, and the patient's clothes covering the region of breasts and ovaries of female patients and the testicles of male patients. Measurements were performed for all patients during 1 sagittal irradiation and for the majority of patients during 1 transverse irradiation. RESULTS: The phantom measurements demonstrated that the secondary dose measured on the patients surface can be considered as a good approximation for the dose in adjacent organs. The median dose in critical organs for sagittal irradiation was in the range of 25.8 mGy (eyes) to 1.9 mGy (testicles), and for transverse irradiation in the range of 23.3 mGy (eyes) to 1.3 mGy (testicles). The ratio of median organ doses for sagittal and transverse irradiation was 2.1 for the thyroid gland, 1.1 for the eyes, and 1.5 for the other organs. CONCLUSIONS: The dose in critical organs due to non-coplanar irradiation of the pituitary gland is only a small fraction of the dose delivered to the reference point of the planning target volume. The risk of a radiation-induced tumor and a genetic consequence associated with these small doses is generally less than 1% and 0.1%, respectively.