Influence of total-body mass on the scaling of S-factors for patient-specific, blood-based red-marrow dosimetry.

To perform patient-specific, blood-based red-marrow dosimetry, dose conversion factors (the S factors in the MIRD formalism) have to be scaled by patients' organ masses. The dose to red marrow includes both self-dose and cross-irradiation contributions. Linear mass scaling for the self-irradiation term only is usually applied as a first approximation, whereas the cross-irradiation term is considered to be mass independent. Recently, the need of a mass scaling correction on both terms, not necessarily linear and dependent on the radionuclide, has been highlighted in the literature. S-factors taking into account different mass adjustments of organs are available in the OLINDA/EXM code. In this paper, a general algorithm able to fit the mass-dependent factors S(rm<--tb) and S(rm<--rm) is suggested and included in a more general equation for red-marrow dose calculation. Moreover, parameters to be considered specifically for therapeutic radionuclides such as (131)I, (90)Y and 177Lu are reported. The red-marrow doses calculated by the traditional and new algorithms are compared for (131)I in ablation therapy (14 pts), 177Lu- (13 pts) and (90)Y- (11 pts) peptide therapy for neuroendocrine tumours, and (90)Y-Zevalin therapy for NHL (21 pts). The range of differences observed is as follows: -36% to -10% for (131)I ablation, -22% to 5% for 177Lu-DOTATATE, -9% to 11% for (90)Y-DOTATOC and -8% to 6% for (90)Y-Zevalin. All differences are mostly due to the activity in the remainder of the body contributing to cross-irradiation. This paper quantifies the influence of mass scaling adjustment on usually applied therapies and shows how to derive the appropriate parameters for other radionuclides and radiopharmaceuticals.

High-linear energy transfer (LET) alpha versus low-LET beta emitters in radioimmunotherapy of solid tumors: therapeutic efficacy and dose-limiting toxicity of 213Bi- versus 90Y-labeled CO17-1A Fab' fragments in a human colonic cancer model.

Recent studies suggest that radioimmunotherapy (RIT) with high-linear energy transfer (LET) radiation may have therapeutic advantages over conventional low-LET (e.g., beta-) emissions. Furthermore, fragments may be more effective in controlling tumor growth than complete IgG. However, to the best of our knowledge, no investigators have attempted a direct comparison of the therapeutic efficacy and toxicity of a systemic targeted therapeutic strategy, using high-LET alpha versus low-LET beta emitters in vivo. The aim of this study was, therefore, to assess the toxicity and antitumor efficacy of RIT with the alpha emitter 213Bi/213Po, as compared to the beta emitter 90Y, linked to a monovalent Fab' fragment in a human colonic cancer xenograft model in nude mice. Biodistribution studies of 213Bi- or 88Y-labeled benzyl-diethylene-triamine-pentaacetate-conjugated Fab' fragments of the murine monoclonal antibody CO17-1A were performed in nude mice bearing s.c. human colon cancer xenografts. 213Bi was readily obtained from an "in-house" 225Ac/213Bi generator. It decays by beta- and 440-keV gamma emission, with a t(1/2) of 45.6 min, as compared to the ultra-short-lived alpha emitter, 213Po (t(1/2) = 4.2 micros). For therapy, the mice were injected either with 213Bi- or 90Y-labeled CO17-1A Fab', whereas control groups were left untreated or were given a radiolabeled irrelevant control antibody. The maximum tolerated dose (MTD) of each agent was determined. The mice were treated with or without inhibition of the renal accretion of antibody fragments by D-lysine (T. M. Behr et al., Cancer Res., 55: 3825-3834, 1995), bone marrow transplantation, or combinations thereof. Myelotoxicity and potential second-organ toxicities, as well as tumor growth, were monitored at weekly intervals. Additionally, the therapeutic efficacy of both 213Bi- and 90Y-labeled CO17-1A Fab' was compared in a GW-39 model metastatic to the liver of nude mice. In accordance with kidney uptake values of as high as > or = 80% of the injected dose per gram, the kidney was the first dose-limiting organ using both 90Y- and 213Bi-labeled Fab' fragments. Application of D-lysine decreased the renal dose by >3-fold. Accordingly, myelotoxicity became dose limiting with both conjugates. By using lysine protection, the MTD of 90Y-Fab' was 250 microCi and the MTD of 213Bi-Fab' was 700 microCi, corresponding to blood doses of 5-8 Gy. Additional bone marrow transplantation allowed for an increase of the MTD of 90Y-Fab' to 400 microCi and for 213Bi-Fab' to 1100 microCi, respectively. At these very dose levels, no biochemical or histological evidence of renal damage was observed (kidney doses of <35 Gy). At equitoxic dosing, 213Bi-labeled Fab' fragments were significantly more effective than the respective 90Y-labeled conjugates. In the metastatic model, all untreated controls died from rapidly progressing hepatic metastases at 6-8 weeks after tumor inoculation, whereas a histologically confirmed cure was observed in 95% of those animals treated with 700 microCi of 213Bi-Fab' 10 days after model induction, which is in contrast to an only 20% cure rate in mice treated with 250 microCi of 90Y-Fab'. These data show that RIT with alpha emitters may be therapeutically more effective than conventional beta emitters. Surprisingly, maximum tolerated blood doses were, at 5-8 Gy, very similar between high-LET alpha and low-LET beta emitters. Due to its short physical half-life, 213Bi appears to be especially suitable for use in conjunction with fast-clearing fragments.

Studies on the red marrow dosimetry in radioimmunotherapy: an experimental investigation of factors influencing the radiation-induced myelotoxicity in therapy with beta-, Auger/conversion electron-, or alpha-emitters.

Usually, the red marrow (RM) is the first dose-limiting organ in radioimmunotherapy. However, several studies have obtained only poor correlations between the marrow doses and the resulting toxicities. Furthermore, RM doses are mostly not determined directly but are derived from blood doses by assuming a ratio that is, over time for the respective conjugates, more or less constant between blood and marrow activities. The aim of this study was to determine, in a mouse model, this RM:blood activity ratio for various immunoconjugates, to investigate whether there may be differences between complete IgG and its fragments with various labels ((125/131)I versus (111)In, (88/90)Y, or 213Bi), and to analyze, in more detail, factors other than just total dose, such as dose rate or relative biological effectiveness factors, that may influence the resulting myelotoxicity. The maximum tolerated activities (MTAs) and doses (MTDs) of several murine, chimeric, and humanized immunoconjugates as complete IgG or fragments (F(ab)2 and Fab), labeled with beta(-)-emitters (such as 131I or 90Y), Auger electron-emitters (such as 125I or (111)In), or alpha-emitters (such as 213Bi) were determined in nude mice. Blood counts were monitored at weekly intervals; bone marrow transplantation was performed to support the assumption of the RM as dose-limiting. The radiation dosimetry was derived from biodistribution data of the various conjugates, accounting for cross-organ radiation; besides the major organs, the activities in the blood and bone marrow (and bone) were determined over time. Whereas no significant differences were found for the RM:blood ratios between various IgG subtypes, different radiolabels or various time points, differences were found between IgG and bi- or monovalent fragments: typically, the RM:blood ratios were approximately 0.4 for IgG, 0.8 for F(ab')2, and 1.0 for Fab'. Nevertheless, at the respective MTAs, the RM doses differed significantly between the three conjugates: e.g., with 131I-labeled conjugates, the maximum tolerated activities were 260 microCi for IgG, 1200 microCi for F(ab)2, and 3 mCi for Fab, corresponding to blood doses of 17, 9, and 4 Gy, respectively. However, initial dose rates were 10 times higher with Fab as compared to IgG, and still 3 times higher as compared to F(ab)2; interestingly, all three deliver approximately 4 Gy within the first 24 h. The MTDs of all three conjugates were increased by BMT by approximately 30%. Similar observations were made for 90Y-conjugates. Higher RM doses were tolerated with Auger-emitters than with conventional beta(-)-emitters, whereas the MTDs were similar between alpha- and beta(-)-emitters. In accordance to dose rates never exceeding those occurring at the single injection MTA, two subsequent injections of two doses of 80% of the single shot MTA of 131I- or 90Y-labeled Fab' and two doses of 100% of the single shot MTA of 213Bi-labeled Fab' were tolerated without increased lethality, if administered 24-48 h apart. In contrast, reinjection of bivalent conjugates was not possible within 6 weeks. These data suggest that the RM:blood activity ratios differ between IgG and fragments, although there is no anatomical or physiological explanation for this phenomenon at this point. In contrast to the current opinion, indication for a strong influence of the dose rate (or dose per unit time), not only total dose, on the resulting toxicity is provided, whereas the influence of high-linear energy transfer (alpha and Auger/conversion electrons) versus low-linear energy transfer (beta and gamma) type radiation seems to be much lower than expected from previous in vitro data. The lower myelotoxicity of Auger-emitters is probably due to the short path length of their low-energy electrons, which cannot reach the nuclear DNA if the antibody is not internalized into the stem cells of the RM.

Development and validation of a GEANT4 radiation transport code for CT dosimetry.

The authors have created a radiation transport code using the GEANT4 Monte Carlo toolkit to simulate pediatric patients undergoing CT examinations. The focus of this paper is to validate their simulation with real-world physical dosimetry measurements using two independent techniques. Exposure measurements were made with a standard 100-mm CT pencil ionization chamber, and absorbed doses were also measured using optically stimulated luminescent (OSL) dosimeters. Measurements were made in air with a standard 16-cm acrylic head phantom and with a standard 32-cm acrylic body phantom. Physical dose measurements determined from the ionization chamber in air for 100 and 120 kVp beam energies were used to derive photon-fluence calibration factors. Both ion chamber and OSL measurement results provide useful comparisons in the validation of the Monte Carlo simulations. It was found that simulated and measured CTDI values were within an overall average of 6% of each other.

A model of the prostate gland for use in internal dosimetry.

UNLABELLED: 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.

Radiation dose to the upper spine from therapeutic administrations of iodine-131-sodium iodide.

Thyroid cancer patients sometimes receive conventional external irradiation to the neck in addition to radioactive iodine therapy. In these situations, knowledge of the radiation dose already received by the spine in the neck area from the radioiodine administration can be an aid in treatment planning. This paper gives an estimate of the radiation dose to the upper spine from administration of 3700 MBq of 131I-sodium iodide. Monte Carlo codes used to estimate radiation dose from internal emitters usually give absorbed doses to the whole spine or marrow. One such code was modified to give a dose only to the upper spine region near the thyroid. Calculations assumed a thyroid uptake of 10% of administered activity and retention with a 35-hr effective half-time. Activity in the remainder of the body was assumed to clear with a 6-hr half-time to urine. Under these assumptions, the dose to this upper spine region was about 200 mGy.

Absorbed fractions for electrons and beta particles in spheres of various sizes.

UNLABELLED: The use of electron-emitting radionuclides in tumor imaging and therapy has presented some new challenges to conventional radiation dosimetry. The fraction of electron energy absorbed in most source regions has usually been assumed to be unity. In small structures such as localized tumors or isolated regions containing moderate to high energy electron emitters, however, this may not always be the case. METHODS: Using an extension of Berger's scaled absorbed dose distributions for point sources to represent a spherical geometry, absorbed fractions of electron energy for sources uniformly distributed in spheres of various sizes have been calculated. RESULTS: Beta particle and monoenergetic electron energies studied range from 0.025 to 4.0 MeV and sphere masses range from 0.01 to 1000 g. S values have also been calculated for 90Y, 123I and 131I based on the results of the absorbed fraction calculations. CONCLUSION: These calculated absorbed fractions are valuable in estimating electron energy loss from small spherical structures and may be useful in estimating the radiation dose to these small volumes.

Breast milk excretion of radiopharmaceuticals: mechanisms, findings, and radiation dosimetry.

The excretion of radiopharmaceuticals in breast milk is studied to understand excretion mechanisms and to determine recommended breast feeding interruption times for many compounds based on the radiation absorbed dose estimated. A literature review is summarized, providing information on breast milk excretion of many radiopharmaceuticals, including the observed fractions of administered activity excreted and the disappearance half-times. Radiation doses to the infant and to the mother's breasts have been calculated using mathematical models of the activity clearance into milk, with interruption schedules for the nursing infant derived using a dose criteria of 1 mSv effective dose to the infant. In only 9 of the 25 radiopharmaceuticals considered here is interruption in breast feeding thought necessary. However, in the literature, breast milk concentrations of radiopharmaceuticals and half-times varied considerably between subjects, and individual measurements are encouraged to raise confidence in specific cases. The absorbed dose to the mother's breast approaches 10-20 mGy (1-2 rad) for a few nuclides, but most doses are quite low. Therapeutic administration of 131I-NaI is a special case, for which the breast dose for a 5550 MBq (150 mCi) administration could approach 2 Gy (200 rad). In this article, these data are discussed, with the aim of assisting others in evaluating the significance of administration of radiopharmaceuticals to lactating women. An example of a sampling scheme and calculation to determine dose for a specific patient is also developed.

Re-evaluation of absorbed fractions for photons and electrons in spheres of various sizes.

UNLABELLED: Absorbed fractions for unit density spheres in an infinite unit density medium, previously calculated for photon emitters and electron emitters, were reevaluated with the Monte Carlo codes EGS4 and MCNP4B. METHODS: Activity was assumed to be distributed uniformly throughout the spheres, and absorbed fractions for self-irradiation were calculated at discrete photon and electron energies. RESULTS: For electrons, the codes were in very good agreement with each other (+/-5%) and with published values, except at higher energies in the very smallest spheres, where some differences exceeded 10%. For photons, the codes were again in good agreement with each other but produced results that varied considerably from published MIRD values. For energies <1 MeV and sphere sizes <50 g, the absorbed fractions determined using the Monte Carlo codes were typically 20%-40% higher than values in MIRD 3 and 8. For energies >1 MeV, the Monte Carlo values were sometimes lower than those in the MIRD documents. Recommended values, generally the average results from the 2 Monte Carlo codes, are given for all sphere sizes and energies for both electrons and photons. CONCLUSION: The absorbed fractions calculated using the Monte Carlo codes should replace the older values and are helpful in evaluating tumor doses, doses to small organs, and other situations in which a uniform distribution of activity throughout a spherical structure of unit density can be assumed.

Monte Carlo MCNP-4B-based absorbed dose distribution estimates for patient-specific dosimetry.

UNLABELLED: This study was intended to verify the capability of the Monte Carlo MCNP-4B code to evaluate spatial dose distribution based on information gathered from CT or SPECT. METHODS: A new three-dimensional (3D) dose calculation approach for internal emitter use in radioimmunotherapy (RIT) was developed using the Monte Carlo MCNP-4B code as the photon and electron transport engine. It was shown that the MCNP-4B computer code can be used with voxel-based anatomic and physiologic data to provide 3D dose distributions. RESULTS: This study showed that the MCNP-4B code can be used to develop a treatment planning system that will provide such information in a time manner, if dose reporting is suitably optimized. If each organ is divided into small regions where the average energy deposition is calculated with a typical volume of 0.4 cm(3), regional dose distributions can be provided with reasonable central processing unit times (on the order of 12-24 h on a 200-MHz personal computer or modest workstation). Further efforts to provide semiautomated region identification (segmentation) and improvement of marrow dose calculations are needed to supply a complete system for RIT. It is envisioned that all such efforts will continue to develop and that internal dose calculations may soon be brought to a similar level of accuracy, detail, and robustness as is commonly expected in external dose treatment planning. CONCLUSION: For this study we developed a code with a user-friendly interface that works on several nuclear medicine imaging platforms and provides timely patient-specific dose information to the physician and medical physicist. Future therapy with internal emitters should use a 3D dose calculation approach, which represents a significant advance over dose information provided by the standard geometric phantoms used for more than 20 y (which permit reporting of only average organ doses for certain standardized individuals)

Pattern of uptake and excretion of (18)F-FDG in the lactating breast.

UNLABELLED: Excretion of radiopharmaceuticals into breast milk poses a potential risk to infants and clear recommendations regarding interruption times are required. There are few data available regarding the impact of (18)F-FDG on this issue. With increasing use of PET for oncologic imaging and its potential advantages to nursing mothers because of its short physical half-life compared with other commonly used tumor imaging agents such as (67)Ga and (201)Tl, evaluation of the excretion pattern of this agent in breast milk is important. METHODS: We have evaluated the uptake of FDG in the breasts in 7 women, 6 of whom were lactating and 1 of whom was in early postpartum but had not commenced breast-feeding. Milk samples were obtained from 4 of the lactating women, including serial samples from 1. RESULTS: Significantly increased breast uptake was identified in all lactating breasts but not in 1 breast consistently refused by the nursing infant or in the woman who had not begun breast-feeding after delivery of her child. No qualitative change or semiquantitative estimate of radiotracer uptake in the breast was seen after expression of breast milk. Decay-corrected activity measurable in breast milk ranged from 5.54 to 19.3 Bq/mL/MBq injected. Using a standard model of breast-feeding, the calculated maximum cumulative dose to the infant, 0.085 mSv with no interruption of breast-feeding, is well below the recommended limit of 1 mSv. CONCLUSION: High uptake of FDG in the lactating breast appears to be related to suckling. There is, however, little secretion of activity into breast milk. Accordingly, a higher radiation dose is received by the infant from close contact with the breast than from ingestion of radioactive milk.

Radiation absorbed doses to the walls of hollow organs.

UNLABELLED: Many radiopharmaceuticals are excreted from the body through the gastrointestinal (GI) tract. The doses to the walls of the organs involved often are very significant. As significant fractions of the administered activity pass through them, these organs may receive the highest doses in the body for many radiopharmaceuticals. The absorbed dose to these walled organs, from activity in their contents, is typically calculated as 50% of the average absorbed dose to the contents, for nonpenetrating emissions. The internal surface of the GI tract, and to a certain extent the urinary bladder, is lined with a variable thickness of mucus. In addition, the radiosensitive cell populations (crypt or stem cells) are located at some depth into the mucosa. These two factors suggest that the surface dose, often used to characterize the clinically relevant absorbed doses for walled organs, may represent an overestimate in some cases. METHODS: In this study, the radiation transport code MCNP was used to simulate the deposition of energy from nonpenetrating emissions of several radionuclides of interest: 90Y, 99mTc,123I and 131I. Absorbed doses as a function of distance from the wall-contents interface were calculated for three geometric shapes representing different organs along the routes of excretion. RESULTS: The absorbed dose from nonpenetrating emissions to the sensitive cell populations was consistently lower than estimated by the standard model assumption. The simulated absorbed doses to radiosensitive cells in the GI tract for 99mTc and 123I are tenfold lower; those for 131I are fivefold lower and those for 90Y are 20% lower. CONCLUSION: This study demonstrates that the normally reported dose to the walls of hollow organs probably should be modified to account for the attenuation of these nonpenetrating emissions in the linings of the walls. This study also demonstrates that Monte Carlo codes continue to be useful in the evaluation of the dose to sensitive cells in walled organs.

A model of the peritoneal cavity for use in internal dosimetry.

Several therapeutic and diagnostic techniques involve injection of radioactive material into the peritoneal cavity. Estimation of the radiation dose to the surface of the peritoneum or to surrounding organs is hampered by the lack of a suitable source region in the phantom commonly used for such calculations. We have modified the Fisher-Snyder phantom to include a region representing the peritoneal cavity which may be employed to estimate such radiation doses. A geometric model is described which is coordinated with the existing organ regions in the phantom. Specific absorbed fractions (derived by Monte Carlo techniques) for photon emissions originating within the cavity are listed. Photon S-values for several radionuclides which have been administered intraperitoneally are shown. Dose conversion factors for electrons irradiating the peritoneal cavity wall, from either a thin plane or volume source of activity within the cavity, are also given for several nuclides.

MIRD Pamphlet No. 14: a dynamic urinary bladder model for radiation dose calculations.

The constant-volume urinary bladder model in the standard MIRD phantom has recognized limitations. Various investigators have developed detailed models incorporating more physiologically realistic features such as expanding bladder contents and residual volume, and variable urinary input rate, initial volume and first void time. We have reviewed these published models and have developed a new model incorporating these factors. The model consists of a spherical source with variable volume to simulate the bladder contents and a wall represented by a spherical shell of constant volume. The wall thickness varies as the source expands or contracts. The model provides for variable urine entry rate (three different hydration states), initial bladder contents volume, residual volume and first void time. The voiding schedule includes an extended nighttime gap during which the urine entry rate is reduced to one-half the daytime rate. Radiation dose estimates have been calculated for the bladder wall surface (including photon and electron components) and at several depths in the wall (electron component) for [18F]FDG, 99mTc-DTPA, 99mTc-HEDP, [99mTc]pertechnetate 99mTc-RBCs, 99mTc-glucoheptonate, 99mTc-MAG3, [123I]/[124I]/[131I]OIH and sodium [131I]iodide(Nal). The initial bladder volume and first void time that provide the lowest radiation dose to the bladder wall are determined separately for each compound to give guidance for establishing dose reduction protocols.

Radiation dose from breastfeeding following administration of thallium-201.

UNLABELLED: Radiation exposure to a breast feeding infant was estimated when the mother underwent a nuclear medicine procedure using 201Tl. METHODS: A lactating mother was administered 111 MBq of 201Tl for a brain scan. Breast milk samples were collected over a period of three days, and the rate of 201Tl secretion was determined. The infant was not breast fed during that time. Based on our data, we determined the time-activity function for radioactivity in the breast milk. From these data, and assuming an intake of 1000 ml/day, we calculated the fraction of administered activity that might be taken in by the infant. We also calculated the intake assuming breastfeeding delays of 2, 24, 48, 72, 96 and 500 hr. RESULTS: We calculated the radiation dose to various organs and the effective dose to an infant and a 1-yr-old for breastfeeding delays of 2 to 500 hr. The effective dose to a 1-yr-old from an administration of 111 MBq of 201Tl to the mother ranged from 0.90 mSv to 0.00072 mSv, and the effective dose to a newborn ranged from 1.6 mSv to 0.0013 mSv depending on delay time. CONCLUSION: Our estimates of radiation exposure to an infant from breastfeeding indicate that in this case, a 1-yr-old would have received less than the NCRP's proposed limit on annual effective dose to members of the general public of 1 mSv with a 48-hr delay and no restrictions on holding the child. A newborn would have received less than the proposed infrequent exposure limit of 5 mSv without any delay or restrictions in breastfeeding.

A new osmium-191/iridium-191m radionuclide generator system using activated carbon.

A new osmium-191/iridium-191m (191Os/191mIr) radionuclide generator system has been developed based on the absorption of K2OsCl6 (Os-IV) on 140-230 mesh heat-treated activated carbon. The generator is eluted with pH 2 saline solution containing 0.25 g/l Kl to give 191mIr in good yield. The generator eluent is neutralized to physiologic pH and isotonicity with Tris buffer immediately prior to i.v. injection. No scavenger column is required. As an example, elution of the prototype generator with a 2-ml bolus results in elution of 191mIr in approximately 18% yield with an 191Os breakthrough of only 2 X 10(-4)%/bolus. The prototype generator has consistent performance over a 2-wk period with no change in 191mIr yield or 191Os breakthrough. Loading of up to 1.5 Ci of 191Os results in no observed radiolysis. Continuous elution of this system is also possible with a mean 191mIr yield of 3.7%/ml and a mean 191Os breakthrough of 2 X 10(-5)%/ml at a flow rate of 12 ml/min. This new system represents a readily available source of 191mIr for radioangiography. Adsorbed radiation dose calculations indicate a total-body dose of only 3.9 mrad for a 100 mCi injected bolus.

Contribution of contaminant indium-114m/indium-114 to indium-111 oxine blood dosimetry.

Indium-114m and 114In appear as contaminants in commercial preparations of [111In]oxine at a level of about 0.05% at time of calibration (TOC). The contribution of these contaminants to the radiation absorbed dose from [111In]oxine leukocyte, platelet, and erythrocyte imaging procedures has been evaluated. When the absorbed dose from these contaminants is expressed as a percent of the 111In dose to the same organ from a given procedure, the contaminants contribute an additional 0.16 to 12% of the 111In dose, and in one case, that of the spleen from [111In]oxine labeled erythrocytes, they contribute an additional 33%. Commercial samples of aqueous-based [111In]oxine contain levels of 114mIn/114In sufficient to result in a mild to moderate increase in the absorbed radiation dose to the patient. Strict quality control procedures must be maintained by suppliers to prevent higher contamination levels. It is advisable to avoid using 111In products of this nature later than about 3 days after the time of calibration.

Radiation dosimetry for the adult female and fetus from iodine-131 administration in hyperthyroidism.

Through a study of the iodine kinetics of 127 patients, we have developed radiation dose estimates to major organs and the fetus for patients with varying degrees of hyperthyroidism. We observed a negative correlation between maximum thyroid uptake and biologic half-time of iodine in the thyroid and used this correlation to predict the biologic half-time at fixed values of maximum thyroid uptake. Dose estimates to the bladder, gonads, marrow, thyroid, uterus, and whole body were estimated for maximum thyroid uptakes from 20% to 100%. Bladder dose varied from 0.6 to 1.0 mGy/MBq and dose to the uterus varied from 0.036 to 0.063 mGy/MBq under different model assumptions. Dose estimates to the fetus and fetal thyroid were approximated at all stages of pregnancy. Average fetal dose was a maximum between 0 and 2 mo of pregnancy, with the maximum ranging from 0.048 mGy/MBq to 0.083 mGy/MBq, depending on model assumptions. Some radiation risks for irradiation of the fetus and the fetal thyroid are discussed.

Bremsstrahlung radiation dose in yttrium-90 therapy applications.

UNLABELLED: The bremsstrahlung component of the decay scheme of beta emitters has been traditionally ignored in internal dosimetry calculations. METHODS: We have estimated the radiation dose from the bremsstrahlung component of the decay scheme of 90Y as a function of distance from a point source in a liquid medium and to body organs from distributed sources of 90Y in the liver and spleen. RESULTS: These estimates agree with measurements of bremsstrahlung dose measured in a Rando phantom, and give an estimate of the importance of this contribution to the overall dosimetry. CONCLUSIONS: The bremsstrahlung radiation absorbed dose contribution from an organ to itself is very small compared to that from the beta dose, but the contribution to other organs is not always negligible, especially when large amounts of 90Y may be involved, as in therapy applications.

Contribution to red marrow absorbed dose from total body activity: a correction to the MIRD method.

UNLABELLED: The contribution to red marrow absorbed dose from beta-emitting radionuclides distributed uniformly in the total body can be overestimated using either MIRD 11 or MIRDOSE3. The S value assigned to the red marrow target region from activity distributed in the remainder of the body is of particular concern. The assumption that the specific absorbed fraction for total body irradiating red marrow and other skeletal tissues is the inverse of the total-body mass can result in an inappropriate remainder-of-body contribution to marrow dose. We evaluated differences in the calculation of marrow dose using MIRD 11 and MIRDOSE3 formulations and developed methods to correct the results from either to remove inappropriate contributions. When bone takes up significantly less activity than is predicted from an apportionment of remainder-tissue activity based on mass, the standard remainder-of-body correction may substantially overestimate the electron component of the S value from remainder tissues to red marrow using either MIRD 11 or MIRDOSE3. If bone takes up activity, this contribution is negligible using MIRD 11 S values but remains with MIRDOSE3 S values. This overestimate can be significant, particularly when the residence time of activity in the remainder of the body is much higher than in the red marrow and a different correction is needed. As the ratio of the remainder of body to marrow residence time is lowered, the overestimate becomes less significant. CONCLUSION: In this article, we show the magnitude of this overestimate (which is most important for nuclides with large "nonpenetrating" emission components and for pharmaceuticals that have a large ratio of remainder of body to marrow residence times), show the appropriate corrections to be made in each case, and propose a new method for calculating marrow dose contributions that will avoid this complication in future applications. Because all models give approximate doses for real patients, with uncertainties within those involved in these corrections, we do not suggest that changes be made to existing marrow dose estimates. We suggest only that future calculations be as accurate as possible.