Improving radiation dosimetry with an automated micronucleus scoring system: correction of automated scoring errors.

Radiation dose estimations performed by automated counting of micronuclei (MN) have been studied for their utility for triage following large-scale radiological incidents; although speed is essential, it also is essential to estimate radiation doses as accurately as possible for long-term epidemiological follow-up. Our goal in this study was to evaluate and improve the performance of automated MN counting for biodosimetry using the cytokinesis-block micronucleus (CBMN) assay. We measured false detection rates and used them to improve the accuracy of dosimetry. The average false-positive rate for binucleated cells was 1.14%; average false-positive and -negative MN rates were 1.03% and 3.50%, respectively. Detection errors seemed to be correlated with radiation dose. Correction of errors by visual inspection of images used for automated counting, called the semi-automated and manual scoring method, increased accuracy of dose estimation. Our findings suggest that dose assessment of the automated MN scoring system can be improved by subsequent error correction, which could be useful for performing biodosimetry on large numbers of people rapidly, accurately, and efficiently.

Interventional radiologists have a higher rate of chromosomal damage due to occupational radiation exposure: a dicentric chromosome assay.

OBJECTIVES: There are growing concerns regarding radiation exposure in medical workers who perform interventional fluoroscopy procedures. Owing to the nature of certain interventional procedures, workers may be subjected to partial-body radiation exposure that is high enough to cause local damage. We aimed to investigate the level of radiation exposure in interventional radiologists in South Korea by performing cytogenetic biodosimetry, particularly focusing on partial-body exposure. METHODS: Interventional radiologists (n = 52) completed a questionnaire, providing information about their work history and practices. Blood samples were collected and processed for a dicentric chromosome assay. We determined Papworth's U-value to assess the conformity of dicentrics with the Poisson distribution to estimate the partial-body exposures of the radiologists. RESULTS: Radiologists had a higher number of dicentrics than the normal population and industrial radiographers. Indeed, subjects with a U-value of > 1.96, an indicator of heterogeneous exposure, were observed more frequently; 4.67 ± 0.81% of their body was irradiated at an average dose of 4.64 ± 0.67 Gy. Logistic regression analysis revealed that the total duration of all interventional procedures per week was associated with partial-body exposure levels. CONCLUSIONS: Our findings suggest that interventional radiologists had greater chromosomal damages than those in other occupational groups, and their partial-body exposure levels might be high enough to cause local damage. Use of special dosimeters to monitor partial-body exposure, as well as restricting the time and frequency of interventional procedures, could help reduce occupational radiation exposure. KEY POINTS: • Interventional radiologists had a higher number of dicentrics than the normal population and industrial radiographers. • The level of partial-body exposure of interventional radiologists might be high enough to cause occupational local damage such as a skin cancer in fingers. • Restricting the duration and frequency of interventional procedures might be helpful in reducing occupational radiation exposure.

Assessment of working environment and personal dosimeter-wearing compliance of industrial radiographers based on chromosome aberration frequencies.

Industrial radiographers are exposed to relatively higher doses of radiation than other radiation-exposed workers in South Korea. The objective of our study was to investigate the impact of specific occupational conditions on chromosome aberration frequency and evaluate dosimeter-wearing compliance of industrial radiographers in Korea. We studied individual and occupational characteristics of 120 industrial radiographers working in South Korea and evaluated the frequency of dicentrics and translocations in chromosomes to estimate radiation exposure. The association between working conditions and chromosome aberration frequencies was assessed by Poisson regression analysis after adjusting for confounding factors. Legal personal dosimeter-wearing compliance among workers was investigated by correlation analysis between recorded dose and chromosome aberration frequency. Daily average number of radiographic films used in the last six months was associated with dicentrics frequency. Workers performing site radiography showed significantly higher translocation frequency than those working predominantly in shielded enclosures. The correlation between chromosome aberration frequency and recorded dose was higher in workers in the radiography occupation since 2012 (new workers) than other veteran workers. Our study found that site radiography could affect actual radiation exposure to workers. Controlling these working conditions and making an effort to improve personal dosimeter-wearing compliance among veteran workers as well as new workers may be necessary to reduce radiation exposure as much as possible in their workplace.

Consecutive results of blood cell count and retrospective biodosimetry: useful tools of health protection regulation for radiation workers.

BACKGROUND: Industrial radiography is known to be one of the most vulnerable lines of work among the range of different radiation work. According to the relevant law in Korea, every worker registered in this work should check their blood cell counts every year in addition to their thermoluminescent dosimeter (TLD) doses. Since the law was enacted, however, few follow-up studies have been carried out based on the obtained results. OBJECTIVES: To ascertain the clinical usefulness of complete blood cell count (CBC) results and suggest a proper protocol of health protection for radiation workers. METHODS: After reviewing all the consecutive results of CBC and TLD doses from radiation workers registered nationwide, we selected two groups of high-risk radiation workers, CBC-high risk (CBC-HR) and TLD-high risk (TLD-HR) groups. A control group of unexposed healthy adults was also included. We compared the absorbed doses calculated by cytogenetic biodosimetry among those three groups, and examined possible confounding factors for each group. RESULTS: Both groups of high-risk radiation workers, CBC-HR and TLD-HR, showed higher chromosome aberrations than the control group. In the control group, previous medical history of a CT scan increased the frequency of chromosome aberrations. In contrast, the frequency of chromosome aberrations in the high-risk radiation workers was affected not by the previous CT history but only by the duration of their work. CONCLUSIONS: We ascertain that reviewing consecutive results of blood cell counts and cytogenetic biodosimetry are useful complementary tools to TLD doses for health protection regulation. Several confounding factors including work duration and previous medical history need to be considered for the interpretation of biodosimetry results.

Scavenger receptor CL-P1 mainly utilizes a collagen-like domain to uptake microbes and modified LDL.

BACKGROUND: Collectins are considered to play a role in host defense via complement activation and opsonization, and are composed of a collagen-like domain and a carbohydrate recognition domain (CRD). Collectin placenta 1 (CL-P1) showed scavenger receptor activity as functions in vitro, and has three candidate domains: a coiled-coil domain, a collagen-like domain and CRD. METHODS: We constructed seven types of CL-P1 deletion mutants to determine the site of each ligand binding domain, and observed whether the specific binding to sugar ligand, microbes, or oxidized LDL decreases or not in cells with CL-P1 deletion mutants and CL-P1 containing mutations of amino acid, respectively. RESULTS: CL-P1 mainly interacted with ligands of microbes through the collagen-like domain and it binds a sugar ligand through the CRD. Additionally it could bind oxidized low density lipoprotein (OxLDL) due to the coiled-coil domain as well as the collagen-like domain. This binding study using mutants at three positively charged sites in the collagen-like domain reveals that the site of R496 K499 K502 plays the most important role in ligand binding functions for microbes and OxLDL. CONCLUSIONS: CL-P1 has three unique functional domains: the collagen-like domain mainly acts against most negatively charged ligands, and the CRD specifically does against sugar substances, while the coiled-coil domain additionally acts on modified LDL. GENERAL SIGNIFICANCE: We considered that the binding activity for various ligands due to the association of a coiled-coil domain, a collagen-like domain and/or a CRD in CL-P1, might play a role in physiological functions in the animal body.

Scavenger receptor CL-P1 mediates endocytosis by associating with AP-2µ2.

BACKGROUND: Scavenger receptor CL-P1 (collectin placenta 1) has been found recently as a first membrane-type collectin which is mainly expressed in vascular endothelial cells. CL-P1 can endocytose OxLDL as well as microbes but in general, the endocytosis mechanism of a scavenger receptor is not well elucidated. METHODS: We screened a placental cDNA library using a yeast two-hybrid system to detect molecules associated with the cytoplasmic domain of CL-P1. We analyzed the binding and endocytosis of several ligands in CL-P1 transfectants and performed the inhibition study using tyrphostin A23 which is a specific inhibitor of tyrosine kinase, especially in µ2-dependent endocytosis and the site-directed mutagenesis in the endocytosis YXXΦ motif in CL-P1 cytoplasmic region. Furthermore, the SiRNA study of clathrin, adaptor AP-2 and dynamin-2 during the endocytosis of OxLDL in CL-P1 transfectant cells was carried out. RESULTS: We identified µ2 subunit of the AP-2 adaptor complex as a molecule associated with the cytoplasmic region of CL-P1. We demonstrated that AP-2µ2 was essential for CL-P1 mediated endocytosis of OxLDL in CL-P1 transfectant cells and its endocytosis was also mediated by clathrin, dynamin and adaptin complex molecules. CONCLUSIONS: Tyrosine-based YXXΦ sequences play an important role in CL-P1-mediated OxLDL endocytosis associated with AP-2µ2. GENERAL SIGNIFICANCE: This might be the first finding of the clear endocytosis mechanism in scavenger receptor CL-P1.

Deep Neural Network-Based Automatic Dicentric Chromosome Detection Using a Model Pretrained on Common Objects.

Dicentric chromosome assay (DCA) is one of the cytogenetic dosimetry methods where the absorbed dose is estimated by counting the number of dicentric chromosomes, which is a major radiation-induced change in DNA. However, DCA is a time-consuming task and requires technical expertise. In this study, a neural network was applied for automating the DCA. We used YOLOv5, a one-stage detection algorithm, to mitigate these limitations by automating the estimation of the number of dicentric chromosomes in chromosome metaphase images. YOLOv5 was pretrained on common object datasets. For training, 887 augmented chromosome images were used. We evaluated the model using validation and test datasets with 380 and 300 images, respectively. With pretrained parameters, the trained model detected chromosomes in the images with a maximum F1 score of 0.94 and a mean average precision (mAP) of 0.961. Conversely, when the model was randomly initialized, the training performance decreased, with a maximum F1 score and mAP of 0.82 and 0.873%, respectively. These results confirm that the model could effectively detect dicentric chromosomes in an image. Consequently, automatic DCA is expected to be conducted based on deep learning for object detection, requiring a relatively small amount of chromosome data for training using the pretrained network.

Molecular cloning and functional analysis of scavenger receptor zebrafish CL-P1.

BACKGROUND: Scavenger receptors are generally expressed in macrophages and vascular endothelial cells and some scavenger receptors are thought to contribute to the development of atherosclerosis. METHODS: We cloned the cDNA of a zebrafish CL-P1 (collectin placenta 1) and performed a knockdown study using its antisense morpholino oligonucleotides (MO). RESULTS: Zebrafish CL-P1 (zCL-P1) is 51% identical to human CL-P1 in its amino acid sequence. Microbes and OxLDL bound to zCL-P1 cDNA transfected cells. zCL-P1 mRNA expression gradually increased after 6hours post-fertilization (hpf), reached its highest level at 24hpf, and then decreased, which is similar to the gene expression pattern of Tie-2. The knockdown of zCL-P1 led to an increase in the number of zebrafish embryos with severe morphological abnormalities such as short body lengths and defects in the dorsal aorta at 48hpf. Simultaneous injection of both MO and synthetic zCL-P1 or zVEGF mRNA rescued the abnormal phenotype. CONCLUSIONS: In vivo knockdown study shows that zCL-P1 is implicated in vasculogenesis and those of our in vitro study support its role as a scavenger receptor. GENERAL SIGNIFICANCE: These results suggest that zCL-P1 might be essential for vasculogenesis during the early embryonic phase in bone fish.

The induction of human CL-P1 expression in hypoxia/reoxygenation culture condition and rat CL-P1 after ischemic/reperfusion treatment.

BACKGROUND: Oxidative stress-induced endothelial dysfunction and oxidized low-density lipoprotein (LDL) might play a key role in the pathogenesis of atherosclerosis. We recently identified a vascular endothelial scavenger receptor, collectin placenta 1 (CL-P1), which acts as a receptor for oxidized LDL as well as for microbes. METHODS: We demonstrate how hypoxic and oxidative stress induced CL-P1 expression and compared their effects with the expression of lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), an endothelial scavenger receptor expressed by oxidative stress. RESULTS: Hypoxia/reoxygenation induced CL-P1 mRNA and protein expression in human umbilical vein endothelial cells (HUVECs). The expression of LOX-1 mRNA in these cells peaked slightly at 24 h, while the expression of CL-P1 had an onset at 72 h and was sustained for 120 h after reoxygenation. Furthermore, the exposure of rat carotid artery endothelium to ischemia/reperfusion increased the maximal CL-P1 mRNA expression at 72 h and expression of its protein peaked at 7 days after this treatment. We demonstrate that CL-P1 up-regulation is induced in vitro and in vivo by oxidative stress. GENERAL SIGNIFICANCE: The inducible expression of CL-P1 by oxidative stress might play a crucial role in endothelial dysfunction or chronic activation leading to the pathogenesis of atherosclerosis.

Trapping Alkali Halide Cluster Ions Inside the Cucurbit[7]uril Cavity.

In this study, the distinctive behavior of cucurbit[n]uril (CB[n]), which captures a variety of alkali halide clusters inside the cavity during the droplet evaporation, has been investigated by using ion mobility spectrometry-mass spectrometry. Complexes of CB[7] with various alkali chloride cluster cations or anions generated during the electrospray ionization were studied, and their collision cross-section (CCS) values were obtained to determine whether these clusters were trapped inside the cavity or not. It was found that the clusters smaller than a specific critical size were trapped inside the CB[7] cavity in the gas phase, although trapping of alkali halide clusters at the given concentration is supposed to be unfavorable in solution. We suggest that the rapid solvent evaporation rapidly increases ion concentrations and subsequently forms alkali-chloride contact ion pairs; therefore, it may provide a specific environment to enable the formation of the inclusion complexes.

Application of a semi-automated dicentric scoring system in triage and monitoring occupational radiation exposure.

The dicentric chromosome assay (DCA) is considered the gold standard for radiation biodosimetry, but it is limited by its long dicentric scoring time and need for skilled scorers. The automation of scoring dicentrics has been considered a strategy to overcome the constraints of DCA. However, the studies on automated scoring methods are limited compared to those on conventional manual DCA. Our study aims to assess the performance of a semi-automated scoring method for DCA using ex vivo and in vivo irradiated samples. Dose estimations of 39 blind samples irradiated ex vivo and 35 industrial radiographers occupationally exposed in vivo were estimated using the manual and semi-automated scoring methods and subsequently compared. The semi-automated scoring method, which removed the false positives of automated scoring using the dicentric chromosome (DC) scoring algorithm, had an accuracy of 94.9% in the ex vivo irradiated samples. It also had more than 90% accuracy, sensitivity, and specificity to distinguish binary dose categories reflecting clinical, diagnostic, and epidemiological significance. These data were comparable to those of manual DCA. Moreover, Cohen's kappa statistic and McNemar's test showed a substantial agreement between the two methods for categorizing in vivo samples into never and ever radiation exposure. There was also a significant correlation between the two methods. Despite of comparable results with two methods, lower sensitivity of semi-automated scoring method could be limited to assess various radiation exposures. Taken together, our findings show the semi-automated scoring method can provide accurate dose estimation rapidly, and can be useful as an alternative to manual DCA for biodosimetry in large-scale accidents or cases to monitor radiation exposure of radiation workers.

Transfusion of γ-irradiated blood components to individuals does not compromise the cytogenetic dose assessment.

Most blood components for transfusions are irradiated ex vivo to prevent transfusion-associated graft-versus-host disease (TA-GvHD); this irradiation can potentially affect the cytogenetic dose assessment of patients showing acute radiation syndrome (ARS) with bone marrow suppression or acute anaemia. Whole blood samples from five donors were irradiated with 0, 10 or 25 Gy γ-rays. The mitotic activity of each cultured blood sample was measured by calculating the mitotic index. A dicentric chromosome assay was used to evaluate the chromosomal aberrations and absorbed dose of blood lymphocytes. Mitogenic activity and scorable metaphase spreads were significantly decreased in the blood samples irradiated with 10 and 25 Gy (p < 0.001). Moreover, a significant increase in the mean scores of all types of chromosomal aberrations in the 10 Gy γ-irradiated samples was observed, with the estimated dose being 11.3 Gy (95% CI: 10.67-11.95 Gy); however, we were unable to estimate the exposure dose in the 25 Gy γ-irradiated samples due to a limited number of scorable metaphase spreads. The mitotic index of the 25 Gy γ-irradiated whole blood samples was significantly suppressed by more than 4-log fold. Thus, in the present study, we evaluated the effects of recommended radiation doses in γ-irradiated transplantation blood components using cytogenetic dosimetry. These results suggest that the partial transfusion of blood components to patients with ARS or acute anaemia did not compromise the estimation of the exposure dose using cytogenetic dosimetry.

Chromosome aberration dynamics in breast cancer patients treated with radiotherapy: Implications for radiation biodosimetry.

Although radiological accidents often result in partial-body radiation exposure, most biodosimetry studies focus on estimating whole-body exposure doses. We have evaluated time-dependent changes in chromosomal aberrations before, during, and after localized fractionated radiotherapy. Twelve patients with carcinoma in situ of the breast who underwent identical adjuvant radiation therapy (50 Gy in 25 fractions) were included in the study. Lymphocytes were collected from patients before, during, and after radiotherapy, to measure chromosome aberrations, such as dicentric chromosomes and translocations. Chromosome aberrations were then used to calculate whole- and partial-body biological absorbed doses of radiation. Dicentric chromosome frequencies in all study participants increased during radiotherapy (p < 0.05 in Kruskal-Wallis test). Increases of translocation frequencies during radiotherapy were observed in seven of the twelve patients. The increased levels of dicentric chromosomes and translocations persisted throughout our 1-year follow-up, and evidence of partial-body exposure (such as Papworth's U-value > 1.96) was observed more than 1 year after radiotherapy. We found that cytogenetic biomarkers reflected partial-body fractionated radiation exposure more than 1 year post-exposure. Our findings suggest that chromosome aberrations can be used to estimate biological absorbed radiation doses and can inform medical intervention for individuals suspected of fractionated or partial-body radiation exposure.

RENEB Inter-Laboratory comparison 2017: limits and pitfalls of ILCs.

PURPOSE: In case of a mass-casualty radiological event, there would be a need for networking to overcome surge limitations and to quickly obtain homogeneous results (reported aberration frequencies or estimated doses) among biodosimetry laboratories. These results must be consistent within such network. Inter-laboratory comparisons (ILCs) are widely accepted to achieve this homogeneity. At the European level, a great effort has been made to harmonize biological dosimetry laboratories, notably during the MULTIBIODOSE and RENEB projects. In order to continue the harmonization efforts, the RENEB consortium launched this intercomparison which is larger than the RENEB network, as it involves 38 laboratories from 21 countries. In this ILC all steps of the process were monitored, from blood shipment to dose estimation. This exercise also aimed to evaluate the statistical tools used to compare laboratory performance. MATERIALS AND METHODS: Blood samples were irradiated at three different doses, 1.8, 0.4 and 0 Gy (samples A, C and B) with 4-MV X-rays at 0.5 Gy min-1, and sent to the participant laboratories. Each laboratory was requested to blindly analyze 500 cells per sample and to report the observed frequency of dicentric chromosomes per metaphase and the corresponding estimated dose. RESULTS: This ILC demonstrates that blood samples can be successfully distributed among laboratories worldwide to perform biological dosimetry in case of a mass casualty event. Having achieved a substantial harmonization in multiple areas among the RENEB laboratories issues were identified with the available statistical tools, which are not capable to advantageously exploit the richness of results of a large ILCs. Even though Z- and U-tests are accepted methods for biodosimetry ILCs, setting the number of analyzed metaphases to 500 and establishing a tests' common threshold for all studied doses is inappropriate for evaluating laboratory performance. Another problem highlighted by this ILC is the issue of the dose-effect curve diversity. It clearly appears that, despite the initial advantage of including the scoring specificities of each laboratory, the lack of defined criteria for assessing the robustness of each laboratory's curve is a disadvantage for the 'one curve per laboratory' model. CONCLUSIONS: Based on our study, it seems relevant to develop tools better adapted to the collection and processing of results produced by the participant laboratories. We are confident that, after an initial harmonization phase reached by the RENEB laboratories, a new step toward a better optimization of the laboratory networks in biological dosimetry and associated ILC is on the way.

Rogue cell-like chromosomal aberrations in peripheral blood lymphocytes of interventional radiologists: A case study.

We report two cases of interventional radiologists who had been exposed to radiation while performing fluoroscopically-guided interventional procedures (FGIPs), mainly transcatheter arterial chemoembolization, percutaneous catheter drainage, and percutaneous transhepatic biliary drainage procedures, for over 10 years. They had a unique multi-aberrant cell type with not only high numbers of dicentrics and/or centric rings but also excess acentric double minutes, similar to a rogue cell. As revealed in a self-administered questionnaire, they wore personal dosimeters and protective equipment at all times and used shielding devices during interventional fluoroscopy procedures. However, the exposed dose levels derived from cytogenetic dosimetry were much higher than the doses recorded on their personal dosimeters. A large number of unstable and stable chromosomal aberrations that were found in the peripheral blood lymphocytes of these interventional radiologists might be due to repeated and long-term exposure to ionizing radiation while performing FGIPs. Further investigations of chromosomal aberrations in interventional radiologists may improve the understanding of the long-term effects of radiation exposure on medical personnel.

Validation of the dicentric chromosome assay for radiation biological dosimetry in South Korea.

The dicentric chromosome assay (DCA) is a well-established biodosimetry test to estimate exposure to ionizing radiation. The Korea Institute of Radiological and Medical Sciences (KIRAMS) established a DCA protocol as a medical response to radiation emergencies in South Korea. To maintain its accuracy and performance, intercomparison exercises with Health Canada (HC) have been conducted; herein, we aimed to validate our capacity of DCA analysis based on those results. Blood samples irradiated at HC were shipped to KIRAMS to assess the irradiation dose to blinded samples using conventional DCA full scoring and triage-based techniques (conventional DCA scoring in triage mode and DCA QuickScan method). Actual doses fell within the 95% confidence intervals of dose estimates for 70-100% of the blinded samples in 2015-2018. All methods discriminated binary dose categories, reflecting clinical significance. This DCA can be used as a reliable radiation biodosimetry tool in preparation for radiation accidents in South Korea.

Translocation Frequency in Patients with Repeated CT Exposure: Comparison with CT-Naive Patients.

Epidemiologic studies using clinical indicators are limited in the assessment of the biological effects of low-dose ionizing radiation for medical purposes. We evaluated the biological effect of low-dose radiation by comparing translocation frequencies in patients with repeated computed tomography (CT) exposure and CT-naïve patients. The goal of this prospective case-control study was to determine whether repeated CT exposure is associated with increased frequency in chromosomal translocations. Two cohorts, comprised of case patients with a history of repeated CT exposure and age- and sex-matched CT-naïve control patients (n = 48 per cohort), were consecutively enrolled in this single-institution study. CT-radiation exposure was estimated using dose-length products, and translocation frequencies of peripheral blood lymphocytes were assessed using whole chromosome paints by fluorescence in situ hybridization (FISH). Comparison of translocation frequencies between cases and controls was performed using the Wilcoxon rank sum test (paired samples), and the relationship between cumulative radiation exposure and translocation frequency was assessed using a partial correlation analysis. Translocation frequencies were significantly different between cases and controls (P = 0.0003). The median translocation frequency was 7 [95% confidence interval (CI): 6, 8] for cases and 4 (95% CI: 3, 6) for controls. By using cumulative radiation exposure as the effect variable and translocation frequency as the response variable, we found a significant correlation between cumulative radiation exposure and translocation frequency (r = 0.6579, P < 0.0001). Chromosomal translocations were more frequent with repeated CT-exposed patients than in CT-naïve patients, and a positive dose-response relationship was present between cumulative radiation exposure and translocation frequency.

Internal Dose Assessment after 131I-Iodide Misadministration in a Patient With Incompletely Blocked Thyroid Uptake: Personalized Internal Dose Assessment by Estimating Individual-Specific Biokinetics.

In July 2017, a medical accident occurred in South Korea, in which I-iodide solution was misadministered to the wrong patient. Although the International Commission on Radiological Protection provided internal dose coefficients for iodine for blocked thyroid, they were not reliable enough for determining the dose to the patient (whose thyroid uptake was incompletely blocked) due to a discrepancy in biokinetics. Therefore, a personalized dose assessment was performed to derive the individual-specific dose coefficients for the patient. Initially, the thyroid biokinetics of the patient were statistically clarified by fitting bioassay monitoring results and the corresponding predicted bioassay values, which were calculated repeatedly for varying iodine transfer rates in an iodine biokinetic model. After determining the transfer rate for the patient, the individual-specific dose coefficients were then calculated in accordance with latest recommendations of the International Commission on Radiological Protection. According to the individual-specific biokinetics, the 24 h thyroid uptake fraction of iodine was estimated as 0.52%. The thyroid absorbed dose of the patient was evaluated as 21.2 Gy, which differed greatly (by about 9 Gy) from the dose evaluated simply using the reference data for blocked thyroid uptake. The personalized dose assessment carried out for the patient not only reduced considerable uncertainties in the internal dose calculation, but also improved the reliability of the calculated internal dose by adopting the latest dosimetric data, including specific absorbed fraction values based on voxel phantoms. Through the dose assessment of the patient, the methodology of personalized dose assessment considering individual-specific biokinetics was developed.

Immunolocalization of a novel collectin CL-K1 in murine tissues.

We have recently identified a novel collectin, CL-K1, that may play a role in innate immunity as a member of the collectin family. In this study using mice, we investigated the tissue distribution of CL-K1 for better understanding of its pathophysiological relevance. Real-time PCR analyses demonstrated that CL-K1 mRNA was expressed in all tissues tested. Immunohistochemical analyses demonstrated that CL-K1 was expressed in proximal tubules of kidney, in mucosa of the gastrointestinal tract, and in bronchial glands of bronchioles similar to the localization of SP-A and SP-D in these pulmonary structures. Immunohistochemistry also showed that CL-K1 was highly expressed in hepatocytes around the central veins in liver, which suggests that murine CL-K1 may be mainly produced in the liver and secreted into the blood stream as is human CL-K1. CL-K1 was especially detected in vascular smooth muscle in several types of tissues. In addition, it was also expressed in intestinal Paneth cells, in mesangial cells of kidney, in pancreatic islet D cells, and in neurons of the brain. It is of interest that this profile of CL-K1 expression is unique among the collectins. Together these histological findings may be useful for understanding the biological function of this novel collectin.