https://eprints.ncl.ac.uk/file_store/production/187503/F3CBDFF1-CE60-43F7-AF30-EA88A642F2F4.pdf

Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study

Numerical Initial Value Problems in Ordinary Differential Equations

Sources, Effects and Risks of Ionizing Radiation

Age-dependent doses to members of the public from intake of radionuclides Part 4: Inhalation dose coefficients

The internal dosimetry schema of the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine has provided a broad framework for assessment of the absorbed dose to whole organs, tissue subregions, voxelized tissue structures, and individual cellular compartments for use in both diagnostic and therapeutic nuclear medicine. The schema was originally published in 1968, revised in 1976, and republished in didactic form with comprehensive examples as the MIRD primer in 1988 and 1991. The International Commission on Radiological Protection (ICRP) is an organization that also supplies dosimetric models and technical data, for use in providing recommendations for limits on ionizing radiation exposure to workers and members of the general public. The ICRP has developed a dosimetry schema similar to that of the MIRD Committee but has used different terminology and symbols for fundamental quantities such as the absorbed fraction, specific absorbed fraction, and various dose coefficients. The MIRD Committee objectives for this pamphlet are 3-fold: to restate its schema for assessment of absorbed dose in a manner consistent with the needs of both the nuclear medicine and the radiation protection communities, with the goal of standardizing nomenclature; to formally adopt the dosimetry quantities equivalent dose and effective dose for use in comparative evaluations of potential risks of radiation-induced stochastic effects to patients after nuclear medicine procedures; and to discuss the need to identify dosimetry quantities based on absorbed dose that address deterministic effects relevant to targeted radionuclide therapy.

https://jnm.snmjournals.org/content/jnumed/50/3/477.full.pdf

MIRD Pamphlet No. 21: A Generalized Schema for Radiopharmaceutical Dosimetry—Standardization of Nomenclature

The consideration of risks from medical diagnostic x-ray examinations and their justification commonly relies on estimates of effective dose, although the quantity is actually a health-detriment-weighted summation of organ/tissue-absorbed doses rather than a measure of risk. In its 2007 Recommendations, the International Commission on Radiological Protection (ICRP) defines effective dose in relation to a nominal value of stochastic detriment following low-level exposure of 5.7 × 10−2 Sv−1, as an average over both sexes, all ages, and two fixed composite populations (Asian and Euro-American). Effective dose represents the overall (whole-body) dose received by a person from a particular exposure, which can be used for the purposes of radiological protection as set out by ICRP, but it does not provide a measure that is specific to the characteristics of the exposed individual. However, the cancer incidence risk models used by ICRP can be used to provide estimates of risk separately for males and females, as a function of age-at-exposure, and for the two composite populations. Here, these organ/tissue-specific risk models are applied to estimates of organ/tissue-specific absorbed doses from a range of diagnostic procedures to derive lifetime excess cancer incidence risk estimates; the degree of heterogeneity in the distribution of absorbed doses between organs/tissues will depend on the procedure. Depending on the organs/tissues exposed, risks are generally higher in females and notably higher for younger ages-at-exposure. Comparing lifetime cancer incidence risks per Sv effective dose from the different procedures shows that overall risks are higher by about a factor of two to three for the youngest age-at-exposure group, 0–9 yr, than for 30–39 yr adults, and lower by a similar factor for an age-at-exposure of 60–69 yr. Taking into account these differences in risk per Sv, and noting the substantial uncertainties associated with risk estimates, effective dose as currently formulated provides a reasonable basis for assessing the potential risks from medical diagnostic examinations.

https://iopscience.iop.org/article/10.1088/1361-6498/acbda7/pdf

Effective doses and risks from medical diagnostic x-ray examinations for male and female patients from childhood to old age

In this issue (pages 21-29), Hunt et al report studies in which volunteers consumed lobster from the coastal area of west Cumbria and measurements were made of the absorption of technetium-99. Previously, Hunt and colleagues (1986, 1990, 1993, 1998) have published measurements of the absorption of plutonium-239/240 and americium-241 from Cumbrian winkles, mussels and cockles, and the naturally occurring alpha emitter, polonium-210, from crabmeat. Their principal motivation has been to improve estimates of radiation doses to specific critical groups of seafood consumers in the coastal communities; in so doing they have provided valuable information for more general assessments of dose and risk. Marine discharges of the alpha-emitting actinide nuclides from Sellafield have been dramatically reduced since the 1970s and 1980s and remain low following the introduction of the Enhanced Actinide Removal Plant in 1994 (BNFL 2000). However, the use of this plant to treat stored liquid wastes has led to an increase in discharges of 99Tc (half-life 2.1 × 105 y). While the actinides and 210Po are concentrated particularly by molluscs, including winkles and mussels, 99Tc is seen in greatest concentrations in lobsters (BNFL 2000, FSA/SEPA 2000). Studies suggest that Tc in lobster flesh occurs predominantly as a complex with the metal-binding protein, metallothionein (Knowles et al 1998, Goudard et al 1998). Hunt et al measured 99Tc in urine and faeces from eight volunteers ingesting lobster flesh. Total faecal elimination of 99Tc was shown to be similar to intake while urinary excretion was low. Attempts to estimate absorption to blood on the basis of differences between intake and faecal elimination were largely unsatisfactory; clearly, this method works best when absorption is high and subsequent excretion occurs predominantly in urine. To estimate absorption on the basis of urinary excretion measurements, it was necessary to interpret results using data reported by Beasley et al (1966) for the urinary excretion of 95 mTc by volunteers after administration as pertechnetate. These data showed that urinary excretion over 7 days after intravenous injection accounted for 34% of the administered activity. Thus, an estimate of absorption of 99Tc from lobster flesh could be made on the assumption that the total reaching the blood was three times the levels measured in bulked 7 day urine samples. However, as discussed by Hunt et al, the time-course of excretion reported by Beasley et al (1966) differed from that observed for the two volunteers ingesting lobster for whom 24 h urine samples had been analysed separately. Urinary excretion during the first day after administration as the pertechnetate was a substantially greater proportion of total urinary excretion over 7 days after administration of 95 mTc as pertechnetate than after consumption of 99Tc in lobster flesh. This difference is largely attributable to rapid excretion of Tc entering the circulation as pertechnetate before binding to proteins and other ligands in blood and other tissues can occur. In addition, a slow rate of absorption to blood from lobster could have contributed; urinary excretion by one of the volunteers given lobster was lower on the day of the meal than on the following day. Hunt et al present two estimates of absorption of 99Tc from lobster: first, applying the pertechnetate data directly (i.e. assuming 34% excretion over 7 days) and second, assuming that the rapid component of excretion from the pertechnetate study does not apply (resulting in an assumed 6.7% excretion over 7 days). The fractional absorption (f1) values obtained were 0.2 ± 0.1 and 0.05 ± 0.02 (rounded to one significant figure). Following their normal practice, Hunt et al give full details of experimental results to facilitate data analysis and interpretation. An alternative approach to the use of the data of Beasley et al (1966) might be to compare ratios of urinary excretion during the first 2 days and the following 5 days for the two studies. These ratios were 3-5 for the lobster study and 8 for the pertechnetate study. On this basis, perhaps half of the early rapid excretion in the pertechnetate study can be regarded as peculiar to pertechnetate, and excluding this would suggest a value of 19% total excretion over 7 days. The f1 value for 99Tc from lobster would then be 0.1 ± 0.03, which lies between the two values given by Hunt et al. The International Commission on Radiological Protection (ICRP 1993) currently uses an f1 value of 0.5 to calculate dose coefficients for the ingestion of radioisotopes of Tc by adult members of the public. This estimate of absorption was based on data from animal studies showing that while Tc administered as pertechnetate was well absorbed, incorporation into plant or animal tissues reduced absorption (Sullivan et al 1977, Gerber et al 1989). A change in f1 from 0.5 to 0.1 would result in only a 30% reduction in committed effective dose per unit intake (CED) from ingestion of 99Tc from 6.4 × 10-10 Sv Bq-1 to 4.5 × 10-10 Sv Bq-1. This is because the effective dose is dominated in each case by equivalent doses to regions of the alimentary tract: the stomach and colon contribute 87% of the CED with an f1 of 0.5 and 96% with an f1 of 0.1. Uncertainties in the calculation of doses to the stomach and colon include assumptions made regarding transit times through these regions and the depth of sensitive cells in the epithelial lining. These issues are being addressed in a revision of the ICRP model of the alimentary tract (Metivier 1998). Although CED values for 99Tc are insensitive to changes in f1 value, doses to tissues from absorbed 99Tc (pure s emitter) are directly proportional to the fraction reaching blood. Clearly, interpretation of bioassay data is also dependent on knowledge of absorption to blood. In the calculation of doses to Sellafield critical groups, account can now be taken of specific f1 data obtained by Hunt et al for 99Tc, isotopes of Pu, 241Am and 210Po. It is noteworthy that in the most recently reported dose estimates for the most exposed Sellafield group of seafood consumers (FSA/SEPA 2000), the contributions from 99Tc and actinide nuclides from Sellafield (<100 µSv) was less than that from 210Po attributable to discharges from the Whitehaven phosphate processing plant and probably less than the dose from naturally occurring background levels of 210Po.

Invited editorial: Gut transfer and doses from environmental technetium.

There is a review of the evidence on which the biokinetic parameters are based and an outline of the methodology used to calculate overall variability. It is concluded that the 95% confidence interval spans an order of magnitude with the most probable value of dose about a factor two below the upper 95th percentile. The gut uptake factor is the most important single parameter

Variability in dose per unit intake to adults, children and infants from ingestion of 239Pu

The practical implementation of the International Commission on Radiological Protection’s (ICRP) system of radiological protection requires the availability of appropriate methodology and data. Ove...

The mandate and work of ICRP Committee 2 on doses from radiation exposure.

We welcome Schollnberger and Kaiser’s comments on our review (Little et al. 2012). The biology of radiation-associated athero-sclerosis has been extensively reviewed (Advisory Group on Ionising Radiation 2010; Little et al. 2010). As we stated in our paper, there are “biological data suggesting that many inflammatory end points potentially relevant to circulatory disease may be differentially regulated below and above about 0.5 Gy,” which is why we studied low-to-moderate exposures (Little et al. 2012). Mitchel et al. (2011) and Rodel et al. (2012) support a possible biphasic dose response, as do many other data (Advisory Group on Ionising Radiation 2010; Little et al. 2010).

Schollnberger et al. used multi-model inference (Burnham and Anderson 1998) to assess circulatory disease risk in their analysis of the Life Span Study (LSS) cohort of atomic-bomb survivors who were exposed briefly to radiation (Schollnberger et al. 2012). We doubt that the effect they observed can be simply generalized to studies of other groups, in particular those chronically exposed. More important, most studies do not have information on potential confounders. We judge that the focus should not be to improve statistical modeling techniques, but to critically address the problems of confounding or other bias and to assess low-dose biological mechanisms.

We also question the validity of the threshold models Schollnberger et al. (2012) used. No data suggest a threshold for biological markers relevant to circulatory disease (Advisory Group on Ionising Radiation 2010; Little et al. 2010).

Schollnberger et al. (2012) used older LSS data (Preston et al. 2003) limited to deaths in proximal survivors since 1968; we judge these restrictions to be questionable for circulatory disease end points. In our analyses (Little et al. 2012), we used current LSS data (Shimizu et al. 2010) that show substantially more deaths (12,139 vs. 3,954 for stroke; 14,018 vs. 4,477 for heart diseases), which means the analysis by Schollnberger et al. (2012) has much less statistical power and that some of their inferences are likely inconsistent with the current data.

In summary, Schollnberger et al. (2012)used biologically questionable models fitted to a single, older (LSS) data set, disregarding evidence from radiation-induced circulatory disease risks in several populations with low-to-moderate exposures (Little et al. 2012). It is important to know whether low doses or dose rates of radiation are associated with increased morbidity and premature mortality and, if so, by what mechanism. The point of our paper was to address this clinical and public health concern.

John Harrison

Papers

Effective doses and risks from medical diagnostic x-ray examinations for male and female patients from childhood to old age

Invited editorial: Gut transfer and doses from environmental technetium.

Variability in dose per unit intake to adults, children and infants from ingestion of 239Pu

The mandate and work of ICRP Committee 2 on doses from radiation exposure.

Estimating Risk of Circulatory Disease: Little et al. Respond.