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Health Concerns Related to Radiation Exposure of the Female Nuclear Medicine Patient

Michael G. Stabin

Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee

• Introduction
• Methods
• Results
• Discussion

Key words: radiation, radiation dosimetry, internal dosimetry, nuclear medicine, women's health issues

This paper is based on a presentation at the International Conference on Radiation and Health held 3-7 November 1996 in Beer Sheva, Israel. Abstracts of these papers were previously published in Public Health Reviews 24(3-4):205-431 (1996). Manuscript received at EHP 11 March 1997; accepted 25 July 1997.

This work was performed for the U.S. Department of Energy under contract DE-AC05-76OR00033, for the U.S. Food and Drug Administration under interagency agreement FDA 224-75-3016, DOE 40-286-71, and for the U.S. Nuclear Regulatory Commission under interagency agreement 1886-0924-A1.

The submitted manuscript has been authored by a contractor of the U.S. government under contract DE-AC05-76OR00033. Accordingly, the U.S. government retains a nonexclusive, royalty-free license to publish or reproduce the published form of the contribution, or allow others to do so, for U.S. government purposes.

Address correspondence to Dr. M.G. Stabin, CHP, Oak Ridge Institute for Science and Education, P.O. Box 117, Oak Ridge, TN 37831-0117. Telephone: 423-576-3449. Fax: 423-576-8673. E-mail: stabinm@orau.gov

Abbreviations used: ED, effective dose; EDE, effective dose equivalent; ICRP, International Commission on Radiological Protection; RIDIC, Radiation Internal Dose Information Center; USNRC, U.S. Nuclear Regulatory Commission.

Introduction

This study provides only estimates of radiation dose for the adult female from nuclear medicine procedures. This information may be used to analyze risks that women might incur from these procedures and to determine how these risks may differ from those incurred by men; such an analysis is outside the scope of this work. Additional information needed to complete such an analysis would include the amount of activity administered per study, the number of studies performed per year, and estimates of the risk incurred per unit of dose received. This information changes frequently and should be obtained at the time any risk-benefit analysis is performed; thus, no attempt was made to include such an analysis in this work.

Methods

A wide variety of nuclear medicine studies (~60) were chosen for the comparative study of organ, gonad, and effective doses between men and women. Standard biokinetic models were taken from ICRP Publication 53 (2) or, in some cases, from internal files at the Radiation Internal Dose Information Center (RIDIC) in Oak Ridge, Tennessee. (This center maintains up-to-date information on the kinetics and dosimetry of radiopharmaceuticals. In addition to keeping abreast of material in the open literature, RIDIC often has access to information on biokinetics or dosimetry of these agents through its support role of the nuclear medicine community.) Estimates of the residence times (3) for all significant source organs were established using standard biokinetic models and employing standard adult male (70 kg) and standard adult female (57 kg) phantoms (5,6) as employed in and entered into the MIRDOSE 3.1 software (4). Radiation doses per unit administered activity to the critical organ (single organ receiving the highest radiation dose), the gonads, and the breast were noted and compared. In these phantoms, the breast tissue represents the female breast tissue; no comparisons were made with the dose to male breast tissue, as the latter is not easily evaluated. Therefore, only the female breast dose was calculated and tabulated simply for information. Effective doses for males and females were also reported and compared.

Results from two recent studies performed by RIDIC were also included in this study--one on radiation dosimetry for the embryo/fetus for the pregnant nuclear medicine patient and one on the dose to the nursing infant for breast-feeding mothers who received radiopharmaceuticals. Extensive detail on the methods used in these two studies are published elsewhere (7,8), so only a brief summary is provided here. For the embryo/fetal dose study , an informal survey of a number of nuclear medicine institutions first was performed to determine what radiopharmaceuticals are commonly administered to women of childbearing age as well as what procedures are used to prevent the inadvertent administration of radiopharmaceuticals to pregnant women. The literature was then studied to find as many sources of information as possible about the placental crossover of radiopharmaceuticals. Much of the available information came from animal studies. Where possible, models of the placental crossover of different radiopharmaceuticals as functions of gestation were developed. Next, residence times for activity in the maternal organs (as used in the comparative studies of organ and gonad doses ) were combined with estimated residence times for the placenta and fetus and used with the four phantoms (adult female in early pregnancy, and at 3-month, 6-month, and 9-month gestation) in the MIRDOSE 3.1 software, (4,6). There are many radiopharmaceuticals that can be administered to women of childbearing age for which no informationabout placental crossover could be found in the literature. In these cases, radiation dose estimates to the fetus were developed using only an estimate of the residence times in the mother's organs. It was not thought prudent to just assume values for placental crossover (e.g., 0.5, 1, 5%) with no literature support. These radiation doses, therefore, may underestimate fetal doses in cases in which significant placental crossover occurs, but at present they represent the best estimates available. The dose to the embryo/fetus is thus reported for many radiopharmaceuticals at these four assumed stages of pregnancy. In the study on breast feeding, values reported in the literature for the excretion of many radiopharmaceuticals in the breast milk of nursing mothers participating in nuclear medicine studies were used in a standard model for nursing that assumed the infant consumed 1000 ml/day of milk, feeding at 3-hr intervals, starting either immediately (3 hr) after the administration of the pharmaceutical or at fixed interruption times (6-hr, 12-hr, 24-hr, etc.). From this analysis, an estimate was obtained of the activity ingested by the infant; the activity ingested was assumed to be quickly and instantaneously absorbed into the bloodstream and thereafter to have biokinetics in the infant similar to that in the adult. Organ residence times were thus assigned, and organ doses and effective dose equivalents [as defined in ICRP Publication 30 (9)] were calculated. Effective dose equivalent (9) instead of the effective dose (1) was used because the study was commissioned by the U.S. Nuclear Regulatory Commission (USNRC), which still uses the effective dose equivalent as its regulatory basis. [The numerical difference between effective dose equivalent and effective dose in nuclear medicine doses is usually very small (10).] The USNRC assigned an acceptable dose level of 1 mSv effective dose equivalent to the infant. If the worst-case dose to the infant did not exceed this amount, no interruption of breast feeding was indicated; otherwise the time interval was calculated for which breast feeding had to be stopped to ensure a dose below this level.

Results

Table 1 shows the actual critical organ doses, gonad doses, and effective doses for the radiopharmaceuticals studied in this report. Table 2 shows the ratios of these quantities for the reference adult female/reference adult male. Table 3 shows the breast doses estimated for the adult female for the radiopharmaceuticals studied in this report. Figures 1 to 3 show plots of these results, in histogram format. Figure 4 shows a plot of the breast doses, also in histogram format. The x axes in Figures 1 and 3 are linear and in Figures 2 and 4 logarithmic.

Figure 1. Frequency plot of the ratios (female/male) of critical organ doses calculated in this study.

Figure 2. Frequency plot of the ratios (female/male) of gonad doses calculated in this study.

Figure 3. Frequency plot of the ratios (female/male) of effective doses calculated in this study.

Figure 4. Frequency plot of the female breast doses calculated in this study.

Table 4 is a summary of absorbed doses to the fetus from administration of radiopharmaceuticals to pregnant women (7). These doses are expressed as absorbed dose to the embryo/fetus per unit activity administered to the mother. Shaded rows in the table indicate that some information was available on placental crossover and was used in the estimates. Table 5 is a summary of the recommendations for possible interruption of breast feeding in the nursing mother given a radiopharmaceutical, given the 1-mSv infant dose criterion. Further details on the dosimetry are given in the USNRC (8).

Discussion

As seen in Table 2 and in Figures 1 and 3, the ratio of the standard female's critical organ doses and effective doses over a wide range of studies is about 1.25, with a relatively small standard deviation (less than 10%). This is reasonable based on the ratio of body weights (57 kg vs 70 kg), which represents about a 20% difference. Individual organ differences vary, but these differences basically represent the effect of the smaller mass. The gonad doses, however, have a mean ratio of about 3.5, with a very wide standard deviation. If a few of the highest gonad dose ratios are omitted (four entries with ratios>10), the mean and standard deviations are 2.6 and 1.67, respectively. Thus, it appears that the gonad dose ratio is typically a factor of 2 to 3, but that it can vary widely. Therefore, a woman carries a somewhat higher radiation burden than her male counterpart, given the same amount of activity administered per study. If the activity given were scaled based on individual body mass, however, at least the critical organ and effective dose differences would be eliminated. This is not routine in nuclear medicine practice. The amount of activity administered is often scaled by body mass in pediatric studies, but in adults, generally the same amount of activity is given, based on a number of criteria, so the differences reported here are generally realized in practice. Breast doses (Table 3, Figure 4) vary widely between procedures, from a few Gy per MBq, to a few tens of mGy per MBq.

Fetal doses for most radiopharmaceuticals, when expressed on the basis of dose to the fetus per unit activity administered to the mother, for most radiopharmaceuticals tend to decrease throughout gestation. As the baby grows, the absorbed fractions for the fetus absorbing radiation from maternal organs will increase, but the baby's increase in mass generally offsets this increase (recall that absorbed dose is energy absorbed per unit mass). Exceptions to this occur in cases in which there is a considerable increase in the placental crossover of the radiopharmaceutical as pregnancy progresses, which increases fetal self-dose. Some exceptions also occur for certain organs in the mother's body for which the specific absorbed fraction increases throughout gestation, notably the liver, lungs, and spleen (6). The doses shown in this report give only the average absorbed dose to the whole fetus; current models do not permit adequate modeling of the dose to individual organs within the fetus, although this may be quite important in many circumstances. Some authors (11,12) have attempted on an individual basis to make such individual organ dose estimates. The most notable of these inquiries is that of Watson (11), who demonstrated clearly the importance of the dose to the fetal thyroid for iodine (especially I-131) administration to women after week 10 of gestation.

The dose estimate analysis for the nursing infant reveals that for many radiopharmaceuticals no interruption of breast feeding is indicated, even given the relatively low effective dose equivalent criterion of 1 mSv EDE and a use of the worst case values of breast milk concentration and elimination half-time. Many radiopharmaceuticals have short physical half-lives and decay quickly after administration. Also, because of their short half-lives and their radiation spectrum, most of these nuclides give a fairly low dose per unit intake. A few of the Tc-99m compounds and one I -123 compound required short interruption periods so as not to exceed the 1-mSv effective dose equivalent value. A difference was seen between in vivo- and in vitro-labeled Tc-99m red blood cells, as the former have a higher assumed fraction of free pertechnetate in the injectate--Tc-99m pertechnetate required a 24-hr interruption to satisfy the dose criterion. The most important compounds in the analysis were I-131 NaI, Ga-67 citrate, and Tl-201 chloride. Because of either their long physical or biological half-times or their high radiation dose per unit intake values, or both, these compounds have the potential for relatively high infant doses, and if these studies are used, cessation of breast feeding is probably indicated.

In summary, it is clear that there are special concerns with regard to the female nuclear medicine patient in the risk/benefit analyses. The most important concerns arise when a woman is either pregnant or breast feeding, but the slightly higher organ and gonad radiation burdens a woman carries compared to her male counterpart are also of interest. A logical extension of this work would be to apply the amount of activity administered per study and the number of nuclear medicine studies performed on men and women for each type of study and to examine the population doses identified in routine nuclear medicine practice. Such information was not available at the time of this writing, but this study provides information that could be used for this analysis should it be undertaken.

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