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Biokinetics underlies the basis for assessment of internal exposures. This paper develops a biokinetic method on simultaneous intake of radionuclides from multiple intake scenarios in internal exposures. With numerical techniques that transform the whole biokinetics between the coupled and decoupled representations of the same problem, this method applies to coupled biokinetics with complex structures and has no restrictions of practical importance on the number of intake scenarios, the number of intake parent radionuclides and decay products, and the complexity of decay relationships between parent and progeny nuclides. For illustration, this method is applied to an assumed case of mixed inhalation and ingestion of weapon-grade plutonium material for reference workers that is focused on Pu and Am. Due to coupled biokinetics between the direct intake and ingrowth parts in different intake pathways, the multiple intake results (the contents of lungs, daily excretions, and cumulative contents) display richer behaviors as compared to single intake cases. This method benefits both the prospective and retrospective assessment of internal exposures for complex intake cases in actual applications.

In this work, the benefits in terms of dose enhancement and dose sparing via radiation shielding are evaluated, for a combined irradiation scheme with sources of 241 Am and tumor-infused with Gd agents, regarding conventional 192 Ir treatment. Monte Carlo simulations using PENELOPE code were implemented for endocavitary brachytherapy geometries, configuring a pelvis phantom of 15 cm radius and 30 cm length. Inside, it was defined cylindrical tumor phantoms of 2 cm radius and 4 cm-6 cm length (simulating initial stages) as well as tumors of extensive volume (2.5 and 3.0 cm radius) and difficult coverage. Tumor phantoms were doped with 68 mM and 138 mM of Gd in order to assess the effects of enhancement and protection based on the concentration and emission energy of the isotope. Obtained results for the first tumor group, shown the feasibility of achieving dose enhancements of 94.3%-117% and 160%-194% for 68 mM and 138 mM of Gd infused into the tumor and irradiation with 241 Am, respectively. Similarly, reduced dose enhancements of 3.5-5.7% y 8.9%-11.2% for 68 mM and 138 mM of Gd are attained with 192 Ir. In terms of dose sparing outer the tumor, the radiation shielding and dose enhancement allowed a higher reduction in the dose by 241 Am of 17%-24% for 68 mM and 21%-32% for 138 mM of Gd, and non-negligible dose sparing are produced too by 192 Ir of 2% and 5% for the same concentration of Gd. For the second tumors group, the combined use of 241Am and Gd agents simultaneously allowed to improve coverage and reduce the healthy tissue dose, showing the obtained results the possibility of achieving coverage of 95% of the prescribed dose in 100% of tumor volume together with dose sparing factor of 6-21% reduction in isodose of the studied point and dose enhancements of 75%-158% at the prescription point., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

In-vivo measurement of Pu/241Am in workers is carried out by placing suitable detector above lungs, liver and skeleton, as major fraction of Pu/Am is transferred to liver and skeleton, after its retention in entry organ. In this work, committed effective dose (CED) corresponding to minimum detectable activity for Type M and Type S 239Pu/241Am deposited in these organs are presented and a monitoring protocol of organ measurement giving lowest CED at different time intervals post inhalation is described. We have observed, for Type M compounds, lung measurement is most sensitive method during initial days after exposure. Liver measurement yields lowest CED between 100 and 5000 d and beyond that bone measurement gives lowest CED. For Type S compounds lung measurement remains most sensitive method even up to 10 000 d post inhalation. This study will be useful for the assessment of CED due to internally deposited 239Pu/241Am in the workers.

An americium solution injected intramuscularly into several nonhuman primates (NHPs) was found to behave differently than predicted by the wound models described in the NCRP Report 156. This was because the injection was made along with a citrate solution, which is known to be more soluble than chlorides, oxides, or nitrates on which the NCRP Report was based. A multi-exponential wound model specific to the injected americium solution was developed based on the retention in the intramuscular sites. The model was coupled with the americium systemic model to interpret the urinary excretion data and assess the intake, and it was determined that the models were adequate to predict early urinary excretion in most cases but unable to predict late urinary excretion. This was attributed to the differences in the systemic handling of americium between humans and nonhuman primates. Information on the type of wounds, solubility, particle size, mass, chemical form, etc., should always be considered when performing wound dosimetry.

The increasing threats of nuclear terrorism have made the development of medical countermeasures a priority for international security. Injectable formulations of diethylenetriaminepentaacetic acid (DTPA) have been approved by the FDA; however, an oral formulation is more amenable in a mass casualty situation. Here, the diethyl ester of DTPA, named C2E2, is investigated for potential as an oral treatment for internal radionuclide contamination. C2E2 was synthesized and characterized using NMR, MS, and elemental analysis. The physiochemical properties of solubility, lipophilicity, and stability were investigated in order to predict its oral bioavailability. Finally, an animal efficacy study was conducted in Sprague Dawley rats pre-contaminated by intramuscular injection with (241)Am(NO3)3 to establish effectiveness of the therapy via the oral route. Synthesis of C2E2 yielded a crystalline powder with high solubility and improved lipophilicity over DTPA. The ester was stable in both simulated gastric and intestinal fluids over the anticipated time course of absorption. Capsules containing C2E2 were demonstrated to be stable for 12 months under accelerated stability conditions. After a single dose, C2E2 enhanced the elimination of (241)Am in a dose-dependent manner. Significant improvement was seen in both total (241)Am decorporation and reduction of (241)Am liver and skeletal burden. C2E2 was concluded to be effective when orally administered to (241)Am-contaminated rats. It may therefore have potential for medical countermeasure in treating humans contaminated with (241)Am or other transuranic elements. An oral capsule or powder for reconstitution may be suitable formulations for future development based on the physiochemical properties and anticipated dose required for efficacy.

Monitoring preparation for internal contamination with actinides (e.g. Pu and Am) is required to assess internal doses at nuclear fuel cycle-related facilities. In this paper, the authors focus on skull counting in case of single-incident inhalation of (241)Am and propose an effective procedure for skull counting with an existing system, taking into account the biokinetic behaviour of (241)Am in the human body. The predicted response of the system to skull counting under a certain counting geometry was found to be only ∼1.0 × 10(-5) cps Bq(-1) 1y after intake. However, this disadvantage could be remedied by repeated measurements of the skull during the late stage of the intake due to the predicted response reaching a plateau at about the 1000th day after exposure and exceeding that in the lung counting. Further studies are needed for the development of a new detection system with higher sensitivity to perform reliable internal dose estimations based on direct measurements., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The biodistribution of plutonium and americium has been studied in a rat model after inhalation of two PuO(2) powders in lungs and extra-pulmonary organs from 3 d to 3 mo. The main difference between the two powders was the content of americium (approximately 46% and 4.5% of total alpha activity). The PuO(2) with a higher proportion of americium shows an accelerated transfer of activity from lungs to blood as compared to PuO(2) with the lower americium content, illustrated by increased urinary excretion and higher bone and liver actinide retention. The total alpha activity measured reflects mostly the americium biological behavior. The activity contained in epithelial lining fluid, recovered in the acellular phase of broncho-alveolar lavages, mainly contains americium, whereas plutonium remains trapped in macrophages. Epithelial lining fluid could represent a transitional pulmonary compartment prior to translocation of actinides to the blood and subsequent deposition in extra-pulmonary retention organs. In addition, differential behaviors of plutonium and americium are also observed between the PuO(2) powders with a higher dissolution rate for both plutonium and americium being obtained for the PuO(2) with the highest americium content. Our results indicate that the biological behavior of plutonium and americium after translocation into blood differ two-fold: (1) for the two actinides for the same PuO(2) aerosol, and (2) for the same actinide from the two different aerosols. These results highlight the importance of considering the specific behavior of each contaminant after accidental pulmonary intake when assessing extra-pulmonary deposits from the level of activity excreted in urine or for therapeutic strategy decisions.

All of the actinides are radioactive. Taken into the body, they damage and induce cancer in bone and liver, and in the lungs if inhaled, and U(VI) is a chemical kidney poison. Containment of radionuclides is fundamental to radiation protection, but if it is breached accidentally or deliberately, decontamination of exposed persons is needed to reduce the consequences of radionuclide intake. The only known way to reduce the health risks of internally deposited actinides is to accelerate their excretion with chelating agents. Ethylendiaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) were introduced in the 1950's. DTPA is now clinically accepted, but its oral activity is low, it must be injected as a Ca(II) or Zn(II) chelate to avoid toxicity, and it is structurally unsuitable for chelating U(VI) or Np(V). Actinide penetration into the mammalian iron transport and storage systems suggested that actinide ions would form stable complexes with the Fe(III)-binding units found in potent selective natural iron chelators (siderophores). Testing of that biomimetic approach began in the late 1970's with the design, production, and assessment for in vivo Pu(IV) chelation of synthetic multidentate ligands based on the backbone structures and Fe(III)-binding groups of siderophores. New efficacious actinide chelators have emerged from that program, in particular, octadentate 3,4,3-LI(1,2-HOPO) and tetradentate 5-LIO(Me-3,2-HOPO) have potential for clinical acceptance. Both are much more effective than CaNa3-DTPA for decorporation of Pu(IV), Am(III), U(VI), and Np(IV,V), they are orally active, and toxicity is acceptably low at effective dosage.

Effect of long-term (during 4 weeks) cincacine administration following single parenteral 241Am intake has been studied on rats depending on method (per oral or parenteral), dosage and time of treatment initiation. Cincacine administration leads to limitation of radionuclide incorporation in the major organs of deposition for the both methods of introduction. At the parenteral 241Am intake in the organism parenteral cincacine administration was found to be more effective compared to per oral cincacine administration even in case of its dose increase by a factor of 6 and 12. At the parenteral introduction of the preparation, time of treatment beginning is more significant than at per oral administration.

Distributions of (239,240)Pu and 241Am in the tissues of Japanese were determined and then compared to those estimated using recent ICRP metabolic models. Intakes by inhalation and ingestion were calculated and used as input to the ICRP-30 model or a combination of the ICRP-66 lung model and the ICRP-67 metabolic model. The (239,240)Pu distribution in the lung, liver, skeleton, kidney, and muscle using the combination ICRP-66 and 67 models agreed well with the measured data. However, the measured plutonium concentration in the spleen was higher than predicted and than found in the kidney or muscle and indicates that the spleen should be treated as a separate organ in the ICRP model. The fractional uptake via ingestion of (239,240)Pu was estimated to be 11% with 5 x 10(-4) as the f1 value. The combination of ICRP-66 and 67 models were adequate descriptors of the organ burdens of 241Am measured in Akita and Niigata district populations. The 241Am ingrowth from 241Pu taken into in the human body contributes 90% of the measured burden.

This study aimed to assess the efficacy of 3,4,3-LI(1,2-HOPO) for reducing uranium, plutonium and americium in rats after intramuscular injection of (U-Pu)O2 particles (MOX). Sixteen rats were contaminated by intramuscular injection of a 1 mg MOX suspension and then treated daily for 7 d with LIHOPO (30 or 200 micromol kg(-1)) or DTPA (30 micromol kg(-1)). LIHOPO was inefficient for removing Pu, Am and U from the wound site. However, it reduced Pu retention in carcass and liver by factors of 2 and 6 respectively, and Am retention in carcass and liver by factors of 10 and 30. In contrast, the effect of LIHOPO on U was to decrease the retention in kidneys by a factor of 75. These results confirm that LIHOPO is a good candidate for use after contamination with MOX, in combination with localised wound lavage or surgical treatment aimed at removing most of the contaminant at the wound site.

Effect of different cincacine doses was studied in rats ingesting americium citrate during 2 weeks. As a result new data showing the possibility and efficacy of per oral cincacine administration at americium intake into digestive tract have been obtained. Dose dependence of cincacine efficacy has been stated for per oral 241Am intake. Preparation administration at a dose of 25 mumol/kg reduces amount of 241Am in skeleton, liver and kidney by 93, 90 and 33%, respectively and is optimum for radionuclide removal from the body and for the prevention of its deposition in organs. Digestive system organs and kidney structure at cincacine administration at a dose of 150 and 300 mumol/kg) to the rats ingesting 241Am have been studied.

The effect of Medetopect, a food additive, on the metabolic kinetics of transuranics (239Pu and 241Am) has been studied experimentally in white mongrel rats following chronic intake by ingestion. The Medetopect application has been shown to be advantageous for reduction of the 239Pu and 241Am absorption from and content of the gastrointestinal tract of the animals.

Biological effects of multiple gamma irradiation combined with incorporated 241Am were studied. A cumulative effect provided by each agent was estimated. The radiation disease development was more serious than that caused by a separate action of each radiation agents in the same doses.

In experiments in rats it was found that 241Am transitory decreases the total cell number and alveolar macrophage's percentage in bronchoalveolar lavage fluid (BALF): increases the macrophages size and nuclear size; and increases acid phosphatase and lactate dehydrogenase activities in BALF. It was suggested that 241Am causes and activation in the alveolar macrophages which probably appears as one of factors provoking lung injuries.

1. The efficacy of ZnDTPA administered in drinking water has been investigated for removing 238Pu and 241Am from the rat after their simultaneous inhalation as nitrates. 2. The continual administration of ZnDTPA 95 mumol kg-1 d-1 over a 21 d interval commencing 1 h after exposure reduced the 238Pu content of the lungs and total body to 2% and 8% of those in untreated animals; the corresponding values for 241Am were 3% and 5%. 3. The continual intakes of 950 mumol kg-1 d-1, intermittent intakes of 3600 mumol kg-1 d-1 and the repeated injection of 30 mumol kg-1 body weight were considered no more effective. 4. All orally administered concentrations of ZnDTPA, commencing 7 d after exposure, reduced the total body contents of 238Pu and 241Am to 17% and 20% of controls by 28 d. 5. Histopathological examination of the kidneys, liver and gastrointestinal tract showed no apparent effects of these treatment protocols. 6. It is concluded that the oral administration of ZnDTPA could be an effective treatment for the removal of inhaled transportable forms of Pu and Am after human exposure.

In the lobster, most of the radionuclides ingested with contaminated food are concentrated in the digestive gland. Americium-241 accumulation in the hepatopancreas of the lobster was studied during the digestive cycle. Fractionations of cytosols at different times after ingestion of radioactive preys were performed by gel permeation chromatography to determine the distribution of 241Am in the different macromolecular components. 241Am was associated with ferritin during the whole digestive cycle. This observation suggests a correlation between 241Am distribution pathways and iron metabolism. The distribution of 241Am present in the other cytosolic proteins followed two major steps of accumulation which may be correlated to the evolution of the two main cellular types playing an important role in the digestive cycle (B and R type cells).

Mixtures of Np, Pu and Am were administered to primates (C. jacchus) by gastric intubation to measure their fractional gastrointestinal absorption (f1 values). The values obtained were about 2 x 10(-3) and 1 x 10(-3), respectively, for Np and Pu administered as the citrate, and 2 x 10(-3) and 6 x 10(-4), respectively, for Pu and Am in potato. The significance of these values in terms of absorption in humans is discussed.

Seventy skeletal malignancies in 44 dogs were identified among 117 beagles injected as young adults with graded dosages of approximately 0.07 to 104 kBq 241Am kg-1 and maintained for lifetime observation. All of these tumors were osteosarcomas except four fibrosarcomas of bone and four chondrosarcomas of bone. Of these 117 animals, 114 survived beyond the minimum age (of 2.79 y) for radiation-induced bone cancer, and all are now dead. An expression was derived that described the dependence of percent occurrence of bone sarcoma on skeletal radiation dose of A = 0.76 + 30D, where A = percent of dogs with skeletal malignancy within any dosage group, D = average skeletal dose (< 3 Gy) at 1 y before death (average skeletal dose was calculated to the presumed start of tumor growth, which we have taken to be 1 y before death), and 0.76 represents the lifetime percent malignant bone tumor response among 132 suitable control dogs in our colony not given any radioactivity. All dosage groups with skeletal doses of > 3 Gy at 1 y before death exhibited close to 100% occurrence and appeared to be beyond the region of linearity. Therefore, they were excluded from the derivation of this expression. Similar analysis of corresponding data for beagles given 226Ra as young adults, excluding the two highest dosage groups in which the bone tumor response was approximately 100%, yielded the expression, A = 0.76 + 4.7D, (D < 20 Gy). A ratio of the coefficients in these two expressions indicates the effectiveness at low radiation doses for bone-cancer induction of 241Am relative to 226Ra, or (30 +/- 2.6)(4.7 +/- 0.47)-1 = 6 +/- 0.8. This compares to the relative effectiveness at low radiation doses that was obtained earlier for a 239Pu:226Ra toxicity ratio of about 16 +/- 5.

One of the features of 241Am metabolism in the beagle dog is a relatively high selective deposition in the thyroid glands, equal to approximately 0.06% of the injected dosage per gram. Retention is prolonged and principally in the interstitial connective tissue. The resulting average dose to the thyroid glands is about 1.42 and 0.76 times that delivered to the skeleton and the liver, respectively. This thyroid dose is much higher than has been reported in people. Although significant morphological changes and reductions in serum thyroxine occurred in this experiment, a significant increase in thyroid neoplasia was not observed.

Chelating agents were tested for removal of simultaneously injected Pu-238 and Am-241 from the rat. The effectiveness of early single chelate injections of Pu-238 retention in tissues decreased in the order 3,4,3-LIHOPO > DFO-HOPO > DTPA > DTPA-DX, and for Am-241 in the order 3,4,3-LIHOPO > DTPA-DX > DTPA >> DFO-HOPO. DTPA-DX showed a special ability to remove Am-241 from the liver. Injected 3,4,3-LIHOPO decreased the contents of Pu-238 in bone and liver to 9 and 3%, respectively, of those in untreated controls. Corresponding values for Am-241 in bone and liver were 30 and 6%, respectively, which indicates that 3,4,3-LIHOPO (unlike DFO-HOPO) is not a plutonium-specific chelator. The effectiveness of prompt single oral treatment with 3,4,3-LIHOPO and DFO-HOPO in reducing retention of actinides was comparable with that of those chelators injected with 1 h delay and at one-third of the oral dose. When 3,4,3-LIHOPO was administered by continuous infusion, a superior effect was achieved with total chelate amounts only slightly exceeding that given as single injection. The retention of PU-238 and Am-241 in bones was reduced to < 5 and 10% of controls, respectively; the contents in the liver were < 2% of controls.

This study has examined the efficacy of ZnDTPA administered in drinking water for removing 238Pu and 241Am from the rat after their simultaneous inhalation as nitrates; the dosage used was 95 mumol kg-1d-1. The continuous administration of ZnDTPA over a 14 d interval, commencing 1 h after exposure, reduced the lung and total body contents of 238Pu to, respectively, 11% and 18% of those in untreated rats; the corresponding values for 241Am were 11% and 14%. After the continuous administration of 95 mumol kg-1 from 4 d to 28 d post exposure, the lung and total body contents of 238Pu were, respectively, 5% and 16% of those in controls; the corresponding values for 241Am were 7% and 19%. Further reductions in the actinide contents of body tissues were found when treatment was extended to 52 d or 76 d. These regimens were as effective as twice weekly injections of 30 mumol kg-1 ZnDTPA commencing at 4 d. After the continuous administration of 95 mumol kg-1 d-1 for 72 d, some pathological changes to the gastrointestinal tract were observed but these were considered to be reparable. It was concluded that further work is required to evaluate the toxicity of the ligand and to establish the optimal treatment regimen.

In order to set limits on environmental and occupational intakes of radionuclides, information is needed on their uptake and metabolism in man. Human data are very limited, particularly for long-lived alpha-emitting isotopes such as those of the actinides. Animal experiments are therefore an important source of data on the distribution of radionuclides in tissues, and the effects of factors such as subject age and the chemical form of elements on gastrointestinal absorption. The NRPB performs experimental programs using mainly rats and guinea pigs. In order to study the gastrointestinal absorption and tissue distribution of plutonium, americium and polonium, a variety of analytical techniques are employed. These include ion exchange and solvent extraction leading to alpha spectrometry and liquid scintillation counting. The investigation of low specific-activity environmental or industrial materials, and the very low bioavailability of elements such as the actinides, means that very low levels of activity have to be measured. Contamination at the dissection and tissue separation stage, as well as during the radiochemistry, has to be rigorously avoided. Where very detailed information is needed on the location of radionuclides within tissues, such as in the study of alpha-emitter distribution in the intestine, autoradiography is used. The application and relevance of different measurement techniques to animal studies will be discussed and examples of the results presented.

The biokinetics of 239Pu and 241Am present in three dust samples obtained from Maralinga were investigated after their deposition in the rat lung. Results were used as an experimental basis for assessing the radiological implications for human exposure. The transfer rates of these actinides to blood in the various dusts differed by 50-fold. The most transportable forms were compatible with a material that had 25% class W and 75% class Y characteristics. The doses per unit intake for adults, children, and infants exposed to an aerosol of 5 microns AMAD were calculated to be, respectively, 0.059, 0.076, and 0.140 mSv Bq-1. The corresponding doses for the least transportable forms were the same as those calculated for a class Y compound, namely 0.036, 0.049, and 0.096 mSv Bq-1. The behavior of the actinides in humans was predicted by combining the transfer rates to blood with mechanical clearance data obtained after volunteers had inhaled 85Sr or 88Y labeled fused aluminosilicate particles. The results suggested that monitoring of 241Am in the chest could be used to advantage for assessing intakes incurred by workers involved with any further decontamination procedures but would be of little practical value for assessing inadvertent public exposure. The paper includes comments on the relevance of the 1990 ICRP recommendations and the proposed new dosimetric model for the respiratory tract.

With DTPA as a comparison, the siderophore analogue code named 3,4,3-LIHOPO has been tested for its ability to remove 238Pu and 241Am from rats after their inhalation or intravenous injection as nitrate. The most effective treatment regimen for inhaled Pu was the repeated administration of 30 mumol kg-1 3,4,3-LIHOPO. By 7 days after exposure, the Pu contents of the lungs and total body were reduced respectively to 2 and 4% of those in untreated animals. These values were six and three times less than when DTPA was administered using the same protocol. For inhaled Am, 3,4,3-LIHOPO and DTPA were considered equally effective, the lung and total body contents being reduced respectively to 13 and 10% of those in controls. Some animals showed slight degenerative changes in the liver and proximal tubules of the kidneys after the repeated administration of 30 mumol kg-1 of 3,4,3-LIHOPO; however these changes were less marked than after DTPA treatment. After the intravenous injection of Pu, the most effective regimen was the single administration of 3 mumol kg-1 3,4,3-LIHOPO. The body content at 7 days was reduced to 7% controls compared with 19% after the repeated administration of 30 mumol kg-1 DTPA. At a dosage of 30 mumol kg-1, 3,4,3-LIHOPO was less effective owing to the higher retention of Pu in the liver. With repeated dosages of 30 mumol kg-1 3,4,3-LIHOPO was more effective than DTPA for the decorporation of Am; the body contents were 16 and 31% of those in controls respectively. Importantly, the body content was still reduced to 28% of control after a single administration of 3 mumol kg-1. The ligand 3,4,3-LIHOPO, which is also superior to other siderophore analogues, could represent a most significant development in the decorporation of Pu and Am.

Adult BALB/c mice, injected with osteosarcomogenic amounts of 241Am (between 40 and 500 Bq/g mouse) showed an impaired mineralization capacity of their femoral bone marrow. This effect persisted until at least 1 year after 241Am injection and was expressed after incubation of bone marrow cells in vitro in conditions allowing osteogenic differentiation. The mineralization capacity of marrow in vitro was evaluated by measurement of 85Sr uptake from the tissue culture medium. Two osteogenic assays were used: in marrow cultured as an intact organ (marrow organ cultures), reduced mineralization was observed in mice given 149 Bq 241Am/g mouse or more (skeletal dose rate of 25 mGy/day), in stromal marrow cells cultured from adherent cell layers and subsequently brought into a three-dimensional (3D) mineralizing condition (stromal 3D cultures), reduced 85Sr uptake was observed from the lowest dose level tested (42 Bq 241Am/g mouse, skeletal dose rate of 7 mGy/day). Taking into account that only a fraction of the skeletal alpha-dose reached the marrow of the femoral diaphyses, marrow organ cultures and stromal 3D cultures exhibited high radiosensitivity to alpha-irradiation in vivo. However, after acute X-irradiation of marrow in vivo or in vitro prior to initiation of the marrow organ cultures, X-ray doses of 4 Gy or higher were needed to significantly impair the mineralization capacity of marrow organ cultures in vitro. Our data demonstrated that the osteogenic cells from the bone marrow are subjected to long-term damage after low doses of continuous alpha-irradiation in vivo.

This paper describes the development of sources, applicators, and techniques that can be used to irradiate rat rectums with continuous irradiation at dose rates of interest in brachytherapy, either with the full circumference of the rectum irradiated, or with half of the circumference shielded from the radiation. The system uses encapsulated 241Am sources, to irradiate rat rectum with 60 keV photons continuously at a dose rate of up to 50 cGy/hr. Details of the design and fabrication of the 241Am sources, the rectal applicator, the dosimetry of the system, and the protocols for preparing and irradiating the rats, and for detecting early rectal injury using histological examination of irradiated rectum are presented. Highly effective shielding (attenuation factors as low as 0.04) of half of the circumference of the rat rectum was achievable. Unidirectional 241Am irradiators for intracavitary brachytherapy offer a unique tool for examining the effects of shielding a portion of the circumference of the rat rectum, on the radiation tolerance of the rectum.

Plutonium-239 or 241Am administered intravenously in the monomeric citrate form was initially deposited in beagle livers principally in the hepatocytes and to a much lesser extent in the sinusoidal macrophages and connective tissues. The initial distribution was quite uniform throughout the hepatic parenchyma; however, at later postinjection intervals, depending on the amount of injected activity, the liver burden became increasingly more focal due to: (1) a progressive shift of the radionuclide from the hepatic epithelium to the macrophages; (2) the movement of such macrophages toward the portal or central regions of the lobule; and (3) the displacement of the older more radioactive tissue by regenerating hepatocytes, which generally have a much lower radionuclide content. The hepatic lesions produced by Pu or Am included: (1) necrosis and degenerative changes that were clinically serious or fatal in some of the animals injected with approximately 107 kBq kg-1; (2) marked structural and circulatory changes resulting from necrosis and focal hepatocyte hyperplasia; (3) a significant incidence of both benign and malignant primary liver tumors. In both Pu- and Am-treated dogs, the most frequently appearing neoplasm was the bile duct adenoma, followed by the cholangiocarcinoma. The most obvious difference between Pu- and Am-induced liver neoplasia was the greater frequency of fibrosarcomas and mast cell sarcomas in the Am-treated groups. Hepatomas were of relatively low frequency in animals with Pu or Am burdens. Although the incidence of bone neoplasia was high among the dogs in these studies, the risk of liver tumors, especially in the Am-treated animals, exceeded that of the skeleton in some of the lower dosage levels where the survival times were long. A risk coefficient of approximately 1200 fatal liver malignancies (10(4) beagle Gy)-1, derived from the dosage groups with long survival times, was calculated for combined Pu and Am animals. The prominence of the liver syndromes in beagles with burdens of Pu or Am indicates that humans with body burdens of 239Pu, 241Am, or other actinide elements may be at risk from radiation effects in the liver, including neoplasia development.

A life-span study on male C57BL mice after injection of various doses of 241Am was conducted. The effects on life span were evaluated and the incidence of tumors was determined by procedures that take competing risks into account. Bone tumors were induced in the mice by injections of 22 and 58 Bq 241Am per g. The mice died early from nonneoplastic diseases at the higher dose levels (190, 373, and 1197 Bq 241Am/g). Additionally, spontaneously occurring tumors such as liver carcinomas, lymphosarcomas, and lymphoreticulosarcomas occurred at an enhanced rate with increasing dose level. The data for survival time after 241Am injection and death with bone tumor were compared to data collected previously for 226Ra-injected mice of the same C57BL strain. This enabled direct comparison in the same strain of the effects of the bone-surface seeker 241Am to the effects of the bone-volume seeker 226Ra. The proportional hazards model was applied and the rate of death with bone tumor was 12.9 +/- 5.2 times higher after 241Am injection than after 226Ra injection if the regression covariate was the average dose to the skeleton. The relative risk was 3.5 +/- 1.7 if regressed on the injected radioactivity. The mortality rate after 241Am injection was 20.4 +/- 3.6 times higher than after 226Ra injection if regressed on average dose to the skeleton.

On the basis of comparison of publications on accidental human intake of americium-241 and animal experimental studies dosimetric characteristics were obtained reflecting the dynamics of accumulation, formation of the dose on the organs and parts of the respiratory tract, as well as of the 24-hour elimination from the organism of the mentioned radionuclide following single, short- and long-term administration of americium-241 from the air. Results were obtained with the use of computers for quantitative modelling of the most complete metabolic transport scheme of americium.

In experiments with albino mongrel rats aged from 2 weeks to 1.5-2 years, the kinetics of 241Am distribution was studied after single intraperitoneal administration thereof. The content of 241Am in the skeleton was shown to decrease and in the liver to increase with age.

The distribution of 239PuO2 (241Am) and BeO (7BeO) within the lungs of rats and dogs after the intratracheal administration was found to follow a normal law. The amplitude of deposition variations reached 98 per cent of the amount administered. It is recommended to group the experimental animals by individual deposition estimates.

The pure carboxylated catechoyl amide LICAM(C) and the calcium and zinc salts of diethylenetriaminepenta-acetic acid (DTPA), were tested for efficacy for removing 238Pu and 241Am from rats after inhalation of the nitrate or intravenous injection of the citrate. The results were compared with the efficacy of methylated LICAM(C) used in previous experiments. It was shown that: (1) after inhalation of 238Pu nitrate, DTPA was far superior to pure LICAM(C); (2) after intravenous injection of 238Pu citrate, the infusion of DTPA plus LICAM(C) was only marginally more effective than DTPA alone; and (3) after inhalation or intravenous injection of 238Pu plus 241Am, the efficacy of pure LICAM(C) was only marginally more effective than the methylated form and neither form was effective for the decorporation of 241Am. It was concluded that DTPA, at present, remains the chelating agent of choice for treating persons accidentally contaminated with transportable forms of Pu and Am.

A new inhalation facility is described which allows any combination of up to 72 rodents ranging in size from the mouse to the guinea pig to be exposed simultaneously. Typically for aerosols of MMD 1.5 microns the initial lung deposit in the rat is 0.05 to 0.07% of the total amount of material used and the coefficient of variation between animals is 15 to 20%.

The efficacies of N1, N5, N10, N14-tetrakis (2,3-dihydroxy-4-carboxybenzoyl)-tetra-azatetradecane [LICAM(C)] and diethylenetriaminepenta-acetic acid (DTPA) (30 mumol/kg body wt.) have been investigated for plutonium (Pu) decorporation after inhalation as the nitrate or tributyl phosphate (TBP) complexes and the data compared with those obtained after its intravenous injection as the citrate. The efficacy of removal of americium (Am) inhaled as the nitrate has also been examined. The results show that: whereas LICAM(C) and DTPA were similarly effective for removing Pu from the blood, LICAM(C) was considerably inferior to DTPA when transportable forms of Pu were inhaled; LICAM(C) is ineffective for the decorporation of Am; the optimum treatment regimen for both Pu and Am involved the prompt and repeated administration of DTPA.

After the inhalation of 238Pu and 241Am as nitrate, the repeated administration of DTPA is far superior to that of LICAM(C) for enhancing their elimination from the body. The therapeutic efficacies of these chelating agents are however similar after intravenous injection of 238Pu as citrate. It is concluded that DTPA should remain the agent of choice for treating persons contaminated internally with transportable forms of these actinides.

Wound contamination was simulated by the intramuscular injections of either 239Pu, 241Am or 244Cm nitrate in the hamster and by the subcutaneous injection of either 239Pu or 241Am nitrate in the rat. The actinides moved from the hamster muscle at approximately the same rate after injection of 370 Bq of each radionuclide (approximate 80 per cent cleared after 6 months). Similarly, the rates of translocation of 239Pu and 241Am in the rat were the same after injection of 370 Bq of each radionuclide (approximate 80 per cent cleared after 1 month). The clearance of 239Pu in the rat was slower after injection of 14.8 kBq and more rapid after injection of 20 Bq (approximately 40 per cent and 90 per cent moved after 1 month, respectively) while the movement of 241Am showed no dependence on the administered dose over the same range. The mixing of 239Pu and 241Am prior to intramuscular injection appeared to enhance the clearance of both radionuclides. The levels of accumulation of each actinide in the skeleton and liver of both species showed that they reached the circulation predominantly in soluble form. Some uptake of Pu and Am in regional lymph nodes was also observed, indicating that lymphatic clearance of polymeric material also took place.

In experiments on Wistar rats a study was made of the carcinogenic effects of the combined exposure to 241Am administered intraperitoneally (6.7 to 229.4 kBq/kg body weight) and external gamma-radiation (137Cs, 175 cGy). The occurrence of osteosarcoma, leucosis, skin and mammary tumors increased in the exposed animals. The combined irradiation produced an additive carcinogenic effect.

Plutonium-239 and americium-241 were administered to adult hamsters in various chemical forms and their absorption from the gut was measured. The results have been compared with published data on other species in order to derive values for the estimated absorption of these actinides in man. On the basis of current knowledge, the best values for adults would appear to be: 0.05% for americium, 0.01% for plutonium ingested in soluble form, and 0.0001% for plutonium ingested as the dioxide. Plutonium dioxide should be considered as soluble if a significant proportion (greater than 5%) of the activity is in particles less than 25 nm in diameter.

The effects of inhaled alpha emitters on the free cell population of the mouse lung were investigated up to 100 days after exposure. Groups of mice inhaled aerosols of 238PuO2, 239PuO2, or 241Am(NO3)3 to give alveolar deposits resulting in lung-averaged cumulative absorbed doses of about 20 Gy by the end of the study. Initially, with 238Pu most of the activity was associated with relatively few pulmonary alveolar macrophages (PAM), whereas with 241Am, all pulmonary alveolar macrophages were labeled and a substantial fraction was extracellular. The free cell population of the lung was sampled using bronchoalveolar lavage. The main parameters investigated were (a) the recovery and total numbers of free cells, including PAM, lymphocytes, and neutrophils; (b) the incidence of nuclear abnormalities in PAM (cells with more than one nucleus or with micronuclei); and (c) metabolic activation of PAM from measurements of their size and associated beta-glucuronidase activity. All three actinides produced depletions in total numbers of PAM, increased incidences of nuclear abnormalities, and metabolic activation of PAM, without a marked infiltration of inflammatory cells. Americium-241, which is distributed relatively uniformly in PAM, produced the most marked changes in that population and 238Pu, which gave the most inhomogeneous distribution of activity, produced the least.

Albino female rats were used in the experiments. After a single intraperitoneal administration of 241Am and 244Cm chloride is doses ranging from 0.37 to 185 kBq/kg (14 doses were used) it was established that the doses applied had different effect on the average life of animals. The largest doses shortened and the lowest increased the life span of experimental animals as compared to the controls. The carcinogenic effect of the studied radionuclides and the development of malignant tumors were detected at sufficiently low doses absorbed. Malignant tumors developed in the experimental and control animals were different not only in their incidence but also their localization and spectrum.