Experimental validation of radiopharmaceutical absorbed dose to mineralized bone tissue

Therapeutic and palliative uses of bone-seeking radiopharmaceuticals are undergoing clinical trials for human subjects. Radiation dosimetry for these applications is based on the Medical Internal Radiation Dosimetry (MIRD) schema. An experimental method for dosimetry of bone tissue based on electron paramagnetic resonance (EPR) spectrometry is described. Preliminary results for beagle bone exposed to radiopharmaceuticals under clinical conditions have indicated that the EPR dose measurements give approximately the calculated dose, but suggest that the dose distribution may be non-uniform.     

Marrow toxicity and radiation absorbed dose estimates from rhenium-186-labeled monoclonal antibody

Estimates of radiation absorbed dose to the red marrow (RM) would be valuable in treatment planning for radioimmunotherapy if they could show a correlation with clinical toxicity. In this study, a correlation analysis was performed to determine whether estimates of radiation absorbed dose to the bone marrow could accurately predict marrow toxicity in patients who had received 186Re-labeled monoclonal antibody. METHODS: White blood cell and platelet count data from 25 patients who received 186Re-NR-LU-10 during Phase I radioimmunotherapy trials were analyzed, and the toxicity grade, the fraction of the baseline counts at the nadir (percentage baseline) and the actual nadir were used as the indicators of marrow toxicity. Toxicity was correlated with various predictors of toxicity. These predictors included the absorbed dose to RM, the absorbed dose to whole body (WB) and the total radioactivity administered. RESULTS: Percentage baseline and grade of white blood cells and platelets all showed a moderate correlation with absorbed dose and radioactivity administered (normalized for body size). The percentage baseline platelet count was the indicator of toxicity that achieved the highest correlation with the various predictors of toxicity (r = 0.73-0.79). The estimated RM absorbed dose was not a better predictor of toxicity than either the WB dose or the total radioactivity administered. There was substantial variation in the blood count response of the patients who were administered similar radioactivity doses and who had similar absorbed dose estimates. CONCLUSION: Although there was a moderately good correlation of toxicity with dose, the value of the dose estimates in predicting toxicity is limited by the patient-to-patient variability in response to internally administered radioactivity. In this analysis of patients receiving 186Re-labeled monoclonal antibody, a moderate correlation of toxicity with dose was observed but marrow dose was of limited use in predicting toxicity for individual patients.     

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.     

The absorbed dose to bone marrow in the treatment of polycythaemia by 32P

This paper reports the determination of absorbed dose to bone marrow in the treatment of polycythaemia by 32P, based on the measurement of activities in bone and marrow biopsies taken at various times from 1 to 27 days after injection of the radionuclide. Activities were measured in the cortex, trabeculation and marrow of biopsies taken from the iliac crest, and slso in sternal marrow. The biological half-life of 32P in marrow from the iliac crest was found to be nine days; that derived for sternal marrow was lower, but the difference was not statistically significant; the value for trabecular bone was 27 days. The biological half life for 32P in the body, as measured by whole-body counting, was 39 days. Calculations of the dose-rate to trabecular marrow have been made by a method based on that of Whitwell and Spiers (1971), but modified to allow for the presence of32P in the marrow as well as in trabecular bone. The dose-rates follow a single exponetial decay with a half-life of 6.7 days. The intergrated dose including that during the first day is 24 rad per mCi injected.     

Mercury exposure from dental amalgam fillings: absorbed dose and the potential for adverse health effects

This review examines the question of whether adverse health effects are attributable to amalgam-derived mercury. The issue of absorbed dose of mercury from amalgam is addressed first. The use of intra-oral Hg vapor measurements to estimate daily uptake must take into account the differences between the collection volume and flow rate of the measuring instrument and the inspiratory volume and flow rate of air through the mouth during inhalation of a single breath. Failure to account for these differences will result in substantial overestimation of the absorbed dose. Other factors that must be considered when making estimates of Hg uptake from amalgam include the accurate measurement of baseline (unstimulated) mercury release rates and the greater stimulation of Hg release afforded by chewing gum relative to ordinary food. The measured levels of amalgam-derived mercury in brain, blood, and urine are shown to be consistent with low absorbed doses (1-3 micrograms/day). Published relationships between the number of amalgam surfaces and urine levels are used to estimate the number of amalgam surfaces that would be required to produce the 30 micrograms/g creatinine urine mercury level stated by WHO to be associated with the most subtle, pre-clinical effects in the most sensitive individuals. From 450 to 530 amalgam surfaces would be required to produce the 30 micrograms/g creatinine urine mercury level for people without any excessive gum-chewing habits. The potential for adverse health effects and for improvement in health following amalgam removal is also addressed. Finally, the issue of whether any material can ever be completely exonerated of claims of producing adverse health effects is considered.     

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.     

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.     

Estimation of absorbed dose to evacuees at pripyat-city using ESR measurements of sugar and exposure rate calculations

Traffic safety in Jordan has been debated in the last few years. A high percentage of the citizens still think that the country is ranked among the most dangerous countries in the world. This study traces the development of traffic safety in Jordan during the last two decades. Examining changes in accident rate over time and comparing with those in Middle Eastern and developing countries, it is concluded that safety levels in Jordan are among the best in Middle Eastern and developing countries.     

Radiation dose to positron emission tomography technologists during quantitative versus qualitative studies

Positron emission tomography technologists were monitored with thermoluminescent dosimeters (TLDs) during qualitative and quantitative studies. Doses to technologists during specific tasks were also measured. The technologists received at least twice as much radiation during the quantitative as the qualitative studies. The average dose per study for qualitative studies was 0.017 mSv (1.7 mrem) shallow and 0.014 mSv (1.4 mrem) deep. The average dose per study for the quantitative studies was 0.05 mSv (5 mrem) shallow and 0.04 mSv (4 mrem) deep. The average dose per study was based on the TLD dose accumulated over studies conducted over four 2-mo and one 1-mo intervals. The dose incurred by the technologists each time they drew a radioactive dose was 0.002 mSv (0.2 mrem) shallow and 0.001 mSv (0.1 mrem) deep. The doses received during injection were 0.014 mSv (1.4 mrem) shallow and 0.007 mSv (0.7 mrem) deep. Doses received during blood sampling were 0.016 mSv (1.6 mrem) shallow and 0.014 mSv (1.4 mrem) deep. During quantitative studies, the technologist received a much greater dose than during its qualitative counterpart due to the blood sampling process and increased time in the room with the radioactive patient.     

On absorbed dose in narrow 60Co gamma-ray beams and dosimetry of the gamma knife

Using separate analytical functions describing primary dose, P0(dm,r), collimator scatter, Sc(r), and phantom scatter, TAR(d,r), an expression for absorbed dose in narrow 60Co gamma-ray beams is developed and each function is quantified: D(d,r) = P0(dm,r) Sc(r) TAR(d,r). The absorbed dose is calculated in beams as narrow as 0.2 cm in radius. Analytical and experimental results are compared using measured dose data for the Gamma Knife. Close agreement with experimental data is observed.     

Regression models for the determination of the absorbed dose rate with an extrapolation chamber for flat ophthalmic applicators

The average surface absorbed dose rate, given by flat ophthalmic applicators (90Sr/90Y, 925 MBq) is determined in equivalent soft tissue using an extrapolation chamber with two flat parallel electrodes of variable separation; the input electrode is fixed in relation to the collector electrode of constant area. When estimating the extrapolation curve slope using a linear regression model, it has been observed that average surface dose rate values were underestimated by up to 19%, as compared to estimations of these values by means of a second degree polynomial regression model, while an improvement of up to 37% is observed in the standard error of the slope in the quadratic model, as compared to that of the linear model. With the aim of validating the results of these models, goodness of fit tests to a Normal (the Shapiro-Wilk test) as well as homogeneity tests on treatment variance (the Bartlett test) were applied. The analysis of variance (ANOVA) tables of fit and residual error breakdown are given: table 3a and 3b for linear fit; 7a and 7b for quadratic fit, and table 10 to error breakdown. Also presented is the global uncertainty of the average dose rate, taking into account the reproducibility of the experimental set-up. It may be inferred that by using this type of measurement for the extrapolation curve slope, quadratic regression models allow for a greater degree of accuracy and precision in determining surface dose rate values. The effective area of the collector electrode and the effective electrode separation in the chamber are also determined by measuring the chamber's electric capacity. Finally, there is an attempt to relate the use of the regression models to the experimental conditions during the measurement of ionization currents (diameter of collector electrode, electrical field gradient, radiation field uniformity, radiation field intensity, etc.). In this particular case, deviations in the distance inverse square law and the "screening" effects during the collection of negative charges (both for primary radiation and the ionization generated by it), are presented as necessary, but insufficient, conditions to explain thoroughly the quadratic behavior of ionizing currents.     

Passage of mannitol from mother to amniotic fluid and fetus

Ten pregnant women and three pregnant sheep received mannitol intravenously. The results show that during late pregnancy this substance appears in amniotic fluid, and when the fetus is alive, its concentration increases with time, reaching values which are higher than those simultaneously obtained in maternal plasma. The experiments performed in sheep show that in fetal urine the concentration of mannitol reached values 10 to 20 times higher than those found in fetal plasma. This supports the hypothesis that the fetal kidney has an important role in the transference of this type of substance from the mother to the amniotic fluid.     

Measurement of the absorbed dose to the patient by computerized whole-body x-ray tomography with the aid of thermoluminescence dosimeters in an Alderson-phantom (author's transl)

Radiation dosis for brain, lung, liver, and kidney examinations which were performed with computerized wholebody scanner (Ohio-Nuclear, 120 KV, 30 mA) was measured by LiF-TLD in the Alderson-Phantom. The absorbed skin dosis to the trunk by a single scan (filtration 6 mm A1) was found to be 1.2 rd at the entrance and 90 mrd at the exit. Patient investigations were simulated with a series of 5 scans. Under those conditions the maximum abdominal entrance dosis is 1.8 rd, at the body axis 700 mrd and near the exit 250 mrd. In this example the dosis to the gonads is less than 2 and 4 mrd, if the distance is more than 15 cm between the last scan and the gonads. Scattered radiation in the Delta-Scan room during an investigation is 1.5 mR/scan and 0.3 mR/scan for a distance of 1 m and 2 m from the irradiated volume.     

Effects of embryo reduction from trichorionic triplets to twins

Sixty-six trichorionic triplet pregnancies reduced to twins were compared with 47 triplet pregnancies that were not reduced. The miscarriage rate was higher (7.6% compared with 2.6%) but the number delivering between 24 and 32 weeks was lower (8.2% compared with 24.0%). Since severe preterm delivery is associated with risks of neonatal death and severe handicap, embryo reduction of triplets to twins may not improve the chance of survival but may reduce the rate of handicap.     

Estimation of the absorbed dose in radiation-processed food--3: The effect of time of evaluation on the accuracy of the estimate

Electron paramagnetic resonance (EPR) spectrometry is evaluated as a method to retrospectively assess the absorbed dose to radiation-processed chicken (containing bone). Decay of the hydroxyapatite paramagnetic center EPR signal intensity was monitored at three different dose levels (0.5, 3.0, 7.0 kGy) up to 20 days, and the dose was assessed for each level at 1, 8, and 20 days after irradiation. It was determined that the time of evaluation (up to 20 days post-irradiation) did not adversely affect the estimate for 0.5 and 3.0 kGy bone, and only moderately affected the 7.0 kGy estimates.