Uncertainty analysis in internal dose calculations for cerium considering the uncertainties of biokinetic parameters and S values.

Radioactive cerium and other lanthanides can be transported through the aquatic system into foodstuffs and then be incorporated by humans. Information on the uncertainty of reported dose coefficients for exposed members of the public is then needed for risk analysis. In this study, uncertainties of dose coefficients due to the ingestion of the radionuclides 141Ce and 144Ce were estimated. According to the schema of internal dose calculation, a general statistical method based on the propagation of uncertainty was developed. The method takes into account the uncertainties contributed by the biokinetic models and by the so-called S values. These S-values were derived by using Monte Carlo radiation transport simulations with five adult non-reference voxel computational phantoms that have been developed at Helmholtz Zentrum München, Germany. Random and Latin hypercube sampling techniques were applied to sample parameters of biokinetic models and S values. The uncertainty factors, expressed as the square root of the 97.5th and 2.5th percentile ratios, for organ equivalent dose coefficients of 141Ce were found to be in the range of 1.2-5.1 and for 144Ce in the range of 1.2-7.4. The uncertainty factor of the detriment-weighted dose coefficient for 141Ce is 2.5 and for 144Ce 3.9. It is concluded that a general statistical method for calculating the uncertainty of dose coefficients was developed and applied to the lanthanide cerium. The dose uncertainties obtained provide improved dose coefficients for radiation risk analysis of humans. Furthermore, these uncertainties can be used to identify those parameters most important in internal dose calculations by applying sensitivity analyses.

Ce-141-labeled DOTMP: A theranostic option in management of pain due to skeletal metastases.

Owing to its favorable radioactive decay characteristics (T1/2  = 32.51 d, Eß [max] = 434.6 keV [70.5%] and 580.0 keV [29.5%], Eγ  = 145.4 keV [48.5%]), 141 Ce could be envisaged as a theranostic radionuclide for use in nuclear medicine. The present article reports synthesis and evaluation of 141 Ce complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylenephosphonic acid (DOTMP) as a potent theranostic agent targeting metastatic skeletal lesions. Ce-141 was produced with 314 ± 29 MBq/mg (n = 6) specific activity and >99.9% radionuclidic purity (n = 6). Around 185 MBq dose of [141 Ce]Ce-DOTMP was synthesized with 98.6 ± 0.5% (n = 4) radiochemical yield under optimized conditions of reaction, and the preparation showed adequately high in vitro stability. Biodistribution studies in normal Wistar rats demonstrated significant skeletal localization and retention of injected activity (2.73 ± 0.28% and 2.63 ± 0.22% of injected activity per gram in femur at 3 hours and 14 days post-injection, respectively) with rapid clearance from non-target organs. The results of biodistribution studies were corroborated by serial scintigraphic imaging studies. These results demonstrate the potential utility of 141 Ce-DOTMP as a theranostic molecule for personalized patient care of cancer patients suffering from painful metastatic skeletal lesions.

Developing the 134Ce and 134La pair as companion positron emission tomography diagnostic isotopes for 225Ac and 227Th radiotherapeutics.

Developing targeted α-therapies has the potential to transform how diseases are treated. In these interventions, targeting vectors are labelled with α-emitting radioisotopes that deliver destructive radiation discretely to diseased cells while simultaneously sparing the surrounding healthy tissue. Widespread implementation requires advances in non-invasive imaging technologies that rapidly assay therapeutics. Towards this end, positron emission tomography (PET) imaging has emerged as one of the most informative diagnostic techniques. Unfortunately, many promising α-emitting isotopes such as 225Ac and 227Th are incompatible with PET imaging. Here we overcame this obstacle by developing large-scale (Ci-scale) production and purification methods for 134Ce. Subsequent radiolabelling and in vivo PET imaging experiments in a small animal model demonstrated that 134Ce (and its 134La daughter) could be used as a PET imaging candidate for 225AcIII (with reduced 134CeIII) or 227ThIV (with oxidized 134CeIV). Evaluating these data alongside X-ray absorption spectroscopy results demonstrated how success relied on rigorously controlling the CeIII/CeIV redox couple.

Fungal spore involvement in the resuspension of radiocaesium in summer.

We observed the atmospheric resuspension of radiocaesium, derived from the Fukushima Dai-ichi Nuclear Power Plant accident, at Namie, a heavily contaminated area of Fukushima, since 2012. During the survey periods from 2012 to 2015, the activity concentrations of radiocaesium in air ranged from approximately 10-5 to 10-2 Bq per m3 and were higher in the warm season than in the cold season. Electron microscopy showed that the particles collected on filters in summer were predominantly of biological origin (bioaerosols), with which the observed radiocaesium activity concentration varied. We conducted an additional aerosol analysis based on fluorescent optical microscopic observation and high-throughput DNA sequencing technique to identify bioaerosols at Namie in 2015 summer. The concentrations of bioaerosols fluctuated the order of 106 particles per m3, and the phyla Basidiomycota and Ascomycota (true Fungi) accounted for approximately two-thirds of the bioaerosols. Moreover, the fungal spore concentration in air was positively correlated with the radiocaesium concentration at Namie in summer 2016. The bioaerosol emissions from Japanese mixed forests in the temperate zone predominately included fungal cells, which are known to accumulate radiocaesium, and should be considered an important scientific issue that must be addressed.

Distribution and Translocation of 141Ce (III) in Horseradish.

BACKGROUND AND AIMS: Rare earth elements (REEs) are used in agriculture and a large amount of them contaminate the environment and enter foods. The distribution and translocation of (141)Ce (III) in horseradish was investigated in order to help understand the biochemical behaviour and toxic mechanism of REEs in plants. METHODS: The distribution and translocation of (141)Ce (III) in horseradish were investigated using autoradiography, liquid scintillation counting (LSC) and electron microscopic autoradiography (EMARG) techniques. The contents of (141)Ce (III) and nutrient elements were analysed using an inductively coupled plasma-atomic emission spectrometer (ICP-AES). RESULTS: The results from autoradiography and LSC indicated that (141)Ce (III) could be absorbed by horseradish and transferred from the leaf to the leaf-stalk and then to the root. The content of (141)Ce (III) in different parts of horseradish was as follows: root > leaf-stalk > leaf. The uptake rates of (141)Ce (III) in horseradish changed with the different organs and time. The content of (141)Ce (III) in developing leaves was greater than that in mature leaves. The results from EMARG indicated that (141)Ce (III) could penetrate through the cell membrane and enter the mesophyll cells, being present in both extra- and intra-cellular deposits. The contents of macronutrients in horseradish were decreased by (141)Ce (III) treatment. CONCLUSIONS: (141)Ce (III) can be absorbed and transferred between organs of horseradish with time, and the distribution was found to be different at different growth stages. (141)Ce (III) can enter the mesophyll cells via apoplast and symplast channels or via plasmodesmata. (141)Ce (III) can disturb the metabolism of macronutrients in horseradish.

Simulation study of light transport in laser-processed LYSO:Ce detectors with single-side readout.

A tightly focused pulsed laser beam can locally modify the crystal structure inside the bulk of a scintillator. The result is incorporation of so-called optical barriers with a refractive index different from that of the crystal bulk, that can be used to redirect the scintillation light and control the light spread in the detector. We here systematically study the scintillation light transport in detectors fabricated using the laser induced optical barrier technique, and objectively compare their potential performance characteristics with those of the two mainstream detector types: monolithic and mechanically pixelated arrays. Among countless optical barrier patterns, we explore barriers arranged in a pixel-like pattern extending all-the-way or half-way through a 20 mm thick LYSO:Ce crystal. We analyze the performance of the detectors coupled to MPPC arrays, in terms of light response functions, flood maps, line profiles, and light collection efficiency. Our results show that laser-processed detectors with both barrier patterns constitute a new detector category with a behavior between that of the two standard detector types. Results show that when the barrier-crystal interface is smooth, no DOI information can be obtained regardless of barrier refractive index (RI). However, with a rough barrier-crystal interface we can extract multiple levels of DOI. Lower barrier RI results in larger light confinement, leading to better transverse resolution. Furthermore we see that the laser-processed crystals have the potential to increase the light collection efficiency, which could lead to improved energy resolution and potentially better timing resolution due to higher signals. For a laser-processed detector with smooth barrier-crystal interfaces the light collection efficiency is simulated to >42%, and for rough interfaces >73%. The corresponding numbers for a monolithic crystal is 39% with polished surfaces, and 71% with rough surfaces, and for a mechanically pixelated array 35% with polished pixel surfaces and 59% with rough surfaces.

Induction in rats of paranasal sinus carcinomas with radioactive cerium chloride.

A colloidal suspension of radioactive cerium stabilized in the form of hydroxide was inoculated into young Sprague-Dawley rats near the maxillary sinus. Well-differentiated epidermoid carcinomas of the paranasal sinus were obtained in 8 of 12 rats and in 8 of 9 animals that liver more then 200 days. Therefore, this istope was highly effectivein inducing tumors at the site of injection. The uniformity of the histologic type of tumors induced under these experimental conditions was remarkable.

Nasal carcinomas in beagles after inhalation of relatively soluble forms of beta-emitting radionuclides.

Beagles were exposed by inhalation to relatively soluble forms of single beta-emitting radionuclides and are being held for life-span observation to evaluate biologic hazards associated with nuclear power production. The dogs were exposed to graded activity levels of 91YCl3, 144CeCl3, or 90SrCl2. With 91YCl3 and 144CeCl3, a significant radiation dose was delivered to the respiratory tract, liver, and skeleton. With 90SrCl2, the dose was almost totally to the skeleton. Squamous cell carcinomas associated with the nasal cavity have been the most frequently observed neoplasms in the 91YCl3 study and one of the most frequent in the 144CeCl3 study, whereas few squamous cell carcainomas have been seen in the 90SrCl2 study. One hemanglosarcoma in the nasal cavity was also seen in the 144Ce study. The incidence of nasal carcinomas may be related to higher relative concentrations of the radionuclides 91Y and 144Ce associated with the nasal turbinates. This relatively high risk of nasal cavity neoplasms suggests that standards for human exposure to these radionuclides should included a consideration of the nasal cavity epithelium as a major target tissue.

Development of a phantom and assessment of (141)Ce as a surrogate radionuclide for flood field uniformity testing of gamma cameras.

This paper describes an indigenous method for development and deployment of rechargeable liquid filled phantom with newly proposed radionuclide (141)Ce for determination of extrinsic uniformity of gamma cameras. Details about design of phantom, neutron irradiation of cerium targets, chemical processing of (141)Ce, charging of phantom with (141)Ce solution and their performance evaluation are presented. Suitability of (141)Ce in quality assurance of gamma cameras used in in-vivo diagnostic imaging procedures has been amply demonstrated.

Nitric oxide influences blood flow distribution in renovascular hypertension.

Endothelium-derived nitric oxide contributes to the regulation of regional blood flow. Inhibition of endothelium-derived nitric oxide synthesis increases blood pressure and vascular resistance. Using the substrate antagonist N omega-nitro-L-arginine-methyl ester to block endothelium-derived nitric oxide synthesis, we tested the hypothesis that, in two-kidney, one clip renovascular hypertension, endothelium-derived nitric oxide plays an increased role in maintaining blood flow to the nonclipped kidney and other visceral organs compared with normotensive controls. This could be due to increased vascular shear stress, a primary stimulus for endothelium-derived nitric oxide synthesis, after the onset of hypertension. In hypertensive rats with mild renal artery stenosis, basal renal blood flow normalized by kidney weight was similar in the nonclipped and clipped kidneys. Basal blood pressure of controls was 98 +/- 2 mm Hg compared with 145 +/- 3 mm Hg in the two-kidney, one clip hypertensive rats. N omega-nitro-L-arginine-methyl ester increased blood pressure by 20 +/- 2 and 43 +/- 3 mm Hg in control and hypertensive rats, respectively. Compared with normotensive controls, basal resistance was higher in all organ beds in the hypertensive rats including brain, heart, intestine, and kidney. With the exception of the renal circulation, the increase in vascular resistance after N omega-nitro-L-arginine-methyl ester was greater in hypertensive rats compared with normotensive controls. In the hypertensive rats, N omega-nitro-L-arginine-methyl ester caused a similar increase in vascular resistance in both the nonclipped and clipped kidneys, and this was not different from normotensive controls.(ABSTRACT TRUNCATED AT 250 WORDS)

The place of brachytherapy in the treatment of carcinoma of the tonsil with lingual extension.

One hundred forty-four of 170 patients (85%) were seen with cancer of the tonsil and received radical irradiation between 1959 and 1980. A 39% crude 3-year disease-free survival rate and a 51% locoregional control rate were observed. Locoregional relapse related to T Stage was 6, 43, 58, and 64% for T1, T2, T3, and T4, respectively. Fifty-four of 144 patients (37%) showed tongue extension, 20% in T1-T2 stages and 50% in T3-T4 stages. Local relapse was 64% and the 3-year disease-free survival rate was 23% in 39 patients with tongue extension treated with external irradiation alone, versus 33 and 43% respectively for 90 patients with no tongue extension. The increase of lymph node metastases or neck recurrences was not related to tongue extension. In 15 patients with tongue extension, treated with external radiation plus brachytherapy, the local relapse was 40% and the 3-year survival rate 60%. External irradiation plus brachytherapy was significantly related to lower local relapse and increased survival rate compared to external irradiation alone in cancer of the tonsil with tongue extension. The combined modality was not associated with increased risk of radiation complications.

Myocardial blood flow as measured by fractional uptake of rubidium-84 and microspheres.

Under conditions of varying flow rates, total myocardial blood flow, measured by fractional uptake of rubidium-84, using a coincidence counting system, was compared with myocardial flow measured by microspheres (15 +/- 5 micrometer). The methods were compared, open-chested, in 47 dogs: 17 during control, ten following 5 min of ligation of left anterior descending coronary artery, five following i.v. isoproterenol, six following ligation and isoproterenol, and nine after ligation plus dipyridamole. Regional flows by Rb-84 and by either Ce-141 or Cr-51 microspheres were also compared for left ventricle, as well as for nonischemic posterior wall, which served as a reference area, and for anterior wall with ligation of left anterior descending artery in the same preparations. There were no significant differences in total or regional flow measured by the two methods, nor in the estimate of ischemic area size. The data indicate that measurement of myocardial blood flow by fractional uptake of a potassium analog is a reliable method in the presence of ischemia and drug intervention. It is suggested that the inequalities of extraction ratio that occur with differing flow rates do not invalidate fractional-uptake methods over the flow ranges examined.

Intramyocardial pressure: effect of preload on transmural distribution of systolic coronary blood flow.

Impairment of systolic coronary blood flow (CBF) may be mediated by intramyocardial pressure (PIM). However, the effect of systole on the magnitude and transmural distribution of coronary blood flow has not been investigated. The purpose of this study was to measure this effect, and, indirectly, intramyocardial pressure. It is assumed that intramyocardial pressure acts on the coronary vessels as a Starling resistor, such that local coronary blood flow is determined by the equation: Coronary perfusion pressure minus intramyocardial pressure equals resistance times coronary blood flow. This equation was integrated with respect to time and solved simultaneously for intramyocardial pressure and resistance by measuring regional coronary blood flow (radioactive microsphere technique) during maximal coronary vasodilatation in two states: beating and hypocalcemic diastolic arrest. Measurements were made in 7 to 16 concentric layers of the left ventricle of 16 dogs. Intramyocardial pressure ranged from near zero to twice peak left ventricular pressure. The transmural distribution of intramyocardial pressure and systolic coronary blood flow depended on preload. The transmural distribution of the ratio of intramyocardial pressure to coronary perfusion pressure was not significantly different from unity across the left ventricular wall at low levels of preload (0 to 4 mm Hg). At moderate to high levels of preload (7 to 35 mm Hg) this ratio was not different from unity (mean 1.03 and 0.96) in the two inner fifths of the left ventricular wall, but was significantly lower (mean 0.79, 0.64 and 0.41, respectively) in the middle and two outer fifths. These data show that intramyocardial pressure shuts off systolic coronary blood flow across the entire left ventricular wall at low levels of preload, and at high levels of preload determines a gradient of decreasing systolic coronary blood flow from the subepicardium to zero in the subendocardial layers. This finding suggests that a dilated or failing left ventricle receives systolic flow to the outer myocardial layers, whereas at low preload levels myocardial perfusion occurs entirely during diastole.

Comparison between measurements of maternal placental blood flow with dynamic placental scintigraphy and radioactive microspheres.

Two methods for measurements of maternal placental blood flow were compared, dynamic placental scintigraphy using 113mIndium and the radioactive microsphere distribution technique which was the reference method. These methods were both used before and after the blood flow was altered by a noradrenaline infusion in pregnant monkeys (Macaca fascicularis). The change of the blood flow values obtained by the two methods were compared. A statistically significant correlation between the two methods was found (r = 0.90, p less than 0.01). It is concluded that dynamic placental scintigraphy can be used as a technique for clinical measurements of relative changes of the maternal placental blood flow.

Osteosarcoma of the nude rat. A model for experimental magnetic resonance imaging studies of bone tumors.

A 144cerium-induced osteosarcoma was transplanted to athymic nude rats (Han:rnu/rnu). Nineteen of the tumor-bearing animals were used to demonstrate the characteristics of the osteosarcoma on magnetic resonance imaging (MRI) in comparison with a group of nine animals that had not received any tumor transplant. The tumor-free animals showed homogeneous results in the measurements of their lower legs (T1, 800-898 mseconds; T2, 33-45 mseconds). The osteosarcomas of the tumor-bearing rats were clearly demonstrated and delineated from adjacent structures by MRI at tumor volumes between 0.3 and 7.5 cm3. A significant increase in T1 and T2 relaxation times was found, which corresponded to the increase in tumor volume. T1 relaxation times decreased slightly when tumor volumes reached greater than 5 cm3, whereas T2 relaxation times remained constant at tumor volumes greater than 2.5 cm3. Histologic changes in the structure of the tumors, occurring naturally during their growth, were proven by immersion-fixed sections embedded in paraffin and stained with hematoxylin-eosin. The water content of small and large tumors was determined by lyophilization and heat drying. Both histologic changes and differences in water content were reflected in the variations of relaxation times.

Validation of regional myocardial flow measurements with scintillation camera detection of xenon-133.

Measurement of disappearance rates of diffusible isotopes with a scintillation camera has been used to estimate myocardial blood flow in man, although there has been no data to assess the accuracy of the technique. We compared regional flow measurements using scintillation camera detection of 133 Xe with essentially simultaneous measurements using gamma-emitter labeled microspheres and differential spectrometry of left ventricular tissue. In 16 dogs, flows through 20--50% of the left ventricle were obtained at rest and with intravenous isoproterenol; the coefficient of correlation of paired measurements with the two techniques was 0.74. In eight dogs, a coronary artery was ligated, and regions approximately 2.2 cm2 at nearby locations in normal, infarcted and marginal tissue studied; the coefficient of correlation was 0.73. In five dogs, flow in three to five precisely identical 1.1 cm2 regions were measured at rest and with isoproterenol by both methods; correlations within each dog ranging from 0.81 to 0.93 were obtained. Although flows with the scintillation camera technique tended to be lower than values with the microsphere technique, it is suggested that the linear correlations of paired values with the two techniques is evidence that scintillation camera detection of 133Xe can be used to quantitate changes in regional myocardial perfusion in the cardiac catheterization laboratory.

Radiation-induced systemic and local bone tumors: two types of late effects with possible different origins?

Bone sarcomas may be induced throughout the skeleton (systemic) in mice by relatively low internal alpha-particle doses that are distributed over the whole skeleton. The induction of local (periosteal) bone sarcomas after paratibial deposition of insoluble radiocolloids required much higher doses, and in addition high energies of emitted particles. Paratibial deposition of alpha-particle-emitting radiocolloids of 227Th and 228Th resulted in formation of both local and systemic bone sarcomas. The latter were most probably induced by the released radium daughters of the thorium isotopes and were distributed about the skeleton. Paratibial injections with beta-particle emitters 144Ce+ 144Pr (29 kBq per mouse) showed an incidence of local bone sarcomas of more than 80%. An estimation of the local effective doses led to values of more than 1000 Gy for the beta-particle emitter 144Ce and around 150 Gy for the thorium isotopes. Thus induction of local bone sarcomas required doses considerably greater than those needed for systemic bone sarcomas. The local induction of bone sarcomas has been reported for high-energy beta particles using similar high doses of 144Ce+ 144Pr in rats and for external 90Sr+ 90Y irradiation in mice. We conclude that the processes involved in the induction of local and systemic bone sarcomas by radiation may be quite different.

Repeated inhalation exposure of rats to aerosols of 144CeO2. I. Lung, liver, and skeletal dosimetry.

To develop a better understanding of the influence of cumulative radiation dose and dose rate to the lungs on the biological responses to inhaled radionuclides, several studies are in progress at this institute in which laboratory animals have been exposed once or repeatedly to aerosols of insoluble particles containing 144Ce or 239Pu. In the study reported here, F344 rats were exposed repeatedly to aerosols of 144CeO2 beginning at 94 days of age to reestablish desired lung burdens of 1.9, 9.2, 46, or 230 kBq of 144Ce every 60 days for 1 year (seven exposures). Other 94-day-old rats were exposed once to achieve similar desired initial lung burdens of 144Ce. Older rats were exposed once to achieve desired initial lung burdens of 46 or 230 kBq when 500 days of age, the age of the repeatedly exposed rats when exposed for the last time. Control rats were either unexposed, sham-exposed once or repeatedly, or exposed once or repeatedly to stable CeO2. Approximately equal numbers of male and female rats were used. The cumulative beta-radiation doses to the lungs, liver, and skeleton of rats exposed repeatedly were similar to those of rats with similar total lung burdens of 144Ce from a single inhalation exposure. The average beta-radiation dose rate to the lungs of the rats exposed repeatedly was about one-fifth of that in rats with similar total lung burdens after a single exposure.

Biological effects of inhaled 144CeCl3 in beagle dogs.

The biological effects of 144Ce were studied in beagle dogs that were exposed to graded activity levels of 144CeCl3 via a single, brief inhalation exposure and observed for their life span. The long-term retained body burdens ranged from 0.06 to 13 MBq/kg with a median of 1.2 MBq/kg. After a short residence time in the lung, most of the 144Ce was translocated to liver and skeleton, where the 144Ce was retained with a half-time approaching the physical half-life of 144Ce, 284 days. Significant radiation doses were delivered to the lung, 28 Gy (median) and 2.5-370 Gy (range); liver, 68 Gy (median) and 6.1-250 Gy (range); and skeleton, 21 Gy (median) and 1.9-100 Gy (range). Lesions induced by the beta-particle radiation were noted in the lung, liver, skeleton, bone marrow, and oral and nasal mucosae closely associated with bone. Early deaths (within 2.5 years) were generally related to hematological dyscrasia, radiation pneumonitis, or hepatocellular degeneration and atrophy. Neoplasms that occurred relatively early, from 2.2-6.8 years after exposure, were noted in the liver, bone, bone marrow and oral mucosa closely associated with bone. Neoplasms that occurred later, beyond 7 years after exposure, were noted in the liver, lung and nasal mucosa closely associated with bone. Increased numbers of neoplasms were not found in two other organs that had relatively high radiation doses, namely the thyroid and kidney. Only one primary bone tumor was noted, but 11 tumors of bone-associated tissues (oral and nasal mucosae and bone marrow) were found. Radiation doses and effects in tissues adjacent to bone, especially those of epithelial or marrow origin, should be considered when determining risks from internally deposited bone-seeking radionuclides, such as 144Ce. The property of 144Ce in depositing on and remaining associated with bone surfaces for long times may be an important factor in the radiation dose to bone marrow and epithelium adjacent to bone.

The toxicity of insoluble cerium-144 inhaled by beagle dogs: non-neoplastic effects.

The biological effects of inhaled beta-particle-emitting radionuclides are not well known. The non-neoplastic diseases induced by an inhaled, relatively insoluble form of cerium-144 ((144)Ce) were studied in beagle dogs exposed to graded activity levels of (144)Ce in fused aluminosilicate particles by a single, brief inhalation exposure and observed for their life span. The initial lung burdens (ILBs) achieved ranged from 0.000093-7.6 MBq (144)Ce/kg body weight. The (144)Ce was retained in the lung with an effective half-life of about 190 days. Significant (144)Ce was translocated to the tracheobronchial lymph nodes, and the concentration exceeded that of the lung at about 400 days after inhalation exposure. Significant radiation doses were delivered to the lung and tracheobronchial lymph nodes and to the heart adjacent to the tracheobronchial lymph nodes. Radiation pneumonitis was the predominant non-neoplastic disease. The dose response for radiation pneumonitis indicated that an ILB of 1.4 MBq/kg would cause death from radiation pneumonitis in 50% of the exposed dogs. This ILB resulted in a pulmonary dose to death of about 350 Gy. The tracheobronchial lymph nodes developed lesions in dogs with ILBs lower than those causing radiation pneumonitis. The overall results of this study, however, showed that (144)Ce, inhaled in an insoluble form, did not cause any unique or inexplicable biological effects in dogs or cause effects at unusually low doses that might call current radiation protection guidelines into question.