Naturally occurring radioactive materials: a method for assessing the risk of exposure

Naturally Occurring Radioactive Materials (NORM) are materials that are found naturally in the environment and contain radioactive isotopes that can cause negative effects on the health of workers who manipulate them. Present in underground work like mining and tunnel construction in granite zones, these materials are difficult to identify and characterize without appropriate equipment for risk evaluation. The assessing methods were exemplified with a case study applied to the handling and processing of phosphoric rock where one found significant amounts of radioactive isotopes and consequently elevated radon concentrations in enclosed spaces containing these materials. © 2015 Taylor & Francis Group, London.

Transfer of radionuclides from soil to vegetation in selected Irish ecosystems

This thesis details the findings of a study relating the transfer of 238U, 228Ra (232Th), 226Ra, and 137Cs from soil to vegetation in an Atlantic blanket bog, upland blanket bog and semi-natural grassland situated along the north-west coast of Ireland. The results of this study provide information on the uptake of these radionuclides by the indigenous vegetation found present in these ecosystems. The ecosystems chosen are internationally recognizable ecosystems and provide a wide variety of vegetation species and contrasting soil physiochemical properties which allow the influence of these parameters on radionuclide uptake to be assessed. The levels of radionuclides in the soil and vegetation were measured using gamma spectrometry, alpha spectrometry and ICP-MS. The nutrient status of the vegetation and soil physiochemical properties were measured using atomic absorption, flame photometry and other analytical techniques. The results of the study indicate that the uptake of 238U and 228Ra (232Th) by vegetation from all three ecosystems was negligible as the levels in all vegetation was below the limits of detection for the methods used in this study. These results appear to indicate that the vegetation studied do not possess the ability to accumulate significant levels of these radionuclides however this assumption cannot be upheld in the case of the Atlantic blanket bog as the levels in the soil of this ecosystem were too low for detection. Similar results were obtained for 226Ra uptake in both the Atlantic blanket bog and grassland for all vegetation with the exception of H. lanatus from the grassland ecosystem. Radium-226 uptake in upland blanket bog was higher and was detectable in the majority of vegetation indigenous to this ecosystem. Transfer factor values ranged from 0.07 to 2.35 and the TF values for E. tetralix were significantly higher than all other vegetation studied. This species of heather demonstrated the ability to accumulate 226Ra to a greater extent than all other vegetation. The uptake of 226Ra by upland blanket bog vegetation appears to be significantly influenced by a range of soil physiochemical properties. The nutrient status of the vegetation, in particular the calcium content in the vegetation appears to have a negative impact on the uptake of this radionuclide. Potassium-40 was detectable in all vegetation present in the three ecosystems and the levels in the grassland soil were significantly higher than the levels in both bogland soils. Transfer factor values for Atlantic blanket bog vegetation ranged from 0.9 to 13 .8 and were significantly higher in E. vaginatum in comparison to C. vulgaris. Potassium-40 TF values for upland blanket bog vegetation on average ranged from 1.4 for C. vulgaris (stems) to 5.2 for E. vaginatum and were statistically similar for all species of vegetation. Transfer factor values for grassland vegetation ranged from 0.7 to 3.8 and were also statistically similar for all species of vegetation indicating that the transfer of 40K to vegetation within the upland bog and grassland ecosystem is not dependent on plant species. Comparisons of 40K TF values for all three ecosystems indicate that the uptake in E. vaginatum from the Atlantic blanket bog was statistically higher than all other vegetation studied. This appears to indicate that E. vaginatum has the ability to accumulate 40K, however, this species of vegetation was also present in the upland blanket and did not demonstrate the same behaviour. The uptake of 40K by vegetation from all three ecosystems was significantly affected by a range of soil physiochemical properties and in some cases the results were contradictory in nature possibly indicating that the affect of these parameters on 40K uptake is species dependent. The most obvious trend in the data was the influence of soil CEC and magnesium levels in vegetation on 40K TF values. A positive correlation was apparent between the CEC of the soil and 40K uptake in vegetation from both the Atlantic blanket bog and grassland ecosystem. A similar trend was apparent between magnesium levels in vegetation and 40K TF values for the upland blanket bog and grassland vegetation. Caesium-13 7 levels were found to be significantly higher in the two bogland soils in comparison to the grassland soil and levels of 137Cs decreased with increasing soil depth. Transfer factor values for Atlantic blanket bog vegetation ranged from 1.9 to 9.6 and TF values were significantly higher in the leaves o f C. vulgaris in comparison to all other vegetation from this ecosystem. Caesium-13 7 TF values for the upland blanket bog vegetation on average ranged from 0.29 for E. tetralix to 1.6 for C. vulgaris. Uptake by the leaves of C. vulgaris was significantly higher than all other vegetation present thereby supporting the trend found within the Atlantic blanket bog vegetation. These results appear to indicate that the leaves of C. vulgaris have the ability to accumulate significant quantities of 137Cs and also that the uptake of 137Cs by this vegetation is dependent on plant compartment as the stems of this vegetation contained significantly lower levels than the leaves in both ecosystems. The uptake of 137Cs by grassland vegetation was very low and was only detectable in a fraction of the vegetation sampled. Caesium-137 TF values for grassland vegetation were in general lower than 0.02. The impact of soil physiochemical properties and nutrient status of vegetation on 137Cs uptake by vegetation appears to be complex and in some cases contradictory. The most apparent trend in the data was the positive influence of vegetation nutrients on 137Cs uptake in particular the magnesium levels present in the vegetation and to a lesser extent the calcium levels present. The results in general indicate that the uptake of 226Ra, 40K and 137Cs by the chosen vegetation is varied and complex and is significantly dependent on the species of vegetation, soil radionuclide concentration, soil physiochemical properties and the nutrient status of the vegetation.

Carcinoembryonic antigen (CEA) in non digestive cancerous and normal tissues.

Carcinoembryonic antigen (CEA), immunologically identical to CEA derived from colonic carcinoma, was identified and purified from perchloric acid (PCA) extracts of bronchial and mammary carcinoma. CEA extracted from bronchial and mammary carcinoma was quantitated by single radial immunodiffusion and was found to be in average about 50-75 times less abundant in these tumors than in colonic carcinoma. CEA could also be detected in one normal breast in lactation and at lower concentrations in normal lung (1000-4000 times lower than in colonic carcinoma). The small amounts of CEA present in normal tissues are distinct from the glycoprotein of small mol. wt showing only partial identity with CEA, that we recently identified and extracted in much larger quantities from normal lung and spleen. The demonstration of the presence of CEA in non digestive carcinoma by classical gel precipitation analysis suggests that the CEA detected in the plasma of such patients by radioimmunoassay is also identical to colonic carcinoma CEA. Our comparative study of plasma CEA from bronchial and colonic carcinoma, showing that CEA from both types of patient has the same elution pattern on Sephadex G-200 and gives parallel inhibition curves in the radioimmunoassay, is in favor of this hypothesis. However, it should not be concluded that all positive CEA radioimmunoassay indicate the presence of an antigen identical to colonic carcinoma CEA. A word of warning concerning the interpretation of radioimmunoassay is required by the observation that the addition of mg amounts of PCA extract of normal plasma, cleared of CEA by Sephadex filtration, could interfere in the test and mimic the presence of CEA.

Predicting hematologic toxicity in patients undergoing radioimmunotherapy with 90Y-ibritumomab tiuxetan or 131I-tositumomab.

This study aimed at identifying clinical factors for predicting hematologic toxicity after radioimmunotherapy with (90)Y-ibritumomab tiuxetan or (131)I-tositumomab in clinical practice. Hematologic data were available from 14 non-Hodgkin lymphoma patients treated with (90)Y-ibritumomab tiuxetan and 18 who received (131)I-tositumomab. The percentage baseline at nadir and 4 wk post nadir and the time to nadir were selected as the toxicity indicators for both platelets and neutrophils. Multiple linear regression analysis was performed to identify significant predictors (P < 0.05) of each indicator. For both platelets and neutrophils, pooled and separate analyses of (90)Y-ibritumomab tiuxetan and (131)I-tositumomab data yielded the time elapsed since the last chemotherapy as the only significant predictor of the percentage baseline at nadir. The extent of bone marrow involvement was not a significant factor in this study, possibly because of the short time elapsed since the last chemotherapy of the 7 patients with bone marrow involvement. Because both treatments were designed to deliver a comparable bone marrow dose, this factor also was not significant. None of the 14 factors considered was predictive of the time to nadir. The R(2) value for the model predicting percentage baseline at nadir was 0.60 for platelets and 0.40 for neutrophils. This model predicted the platelet and neutrophil toxicity grade to within ±1 for 28 and 30 of the 32 patients, respectively. For the 7 patients predicted with grade I thrombocytopenia, 6 of whom had actual grade I-II, dosing might be increased to improve treatment efficacy. The elapsed time since the last chemotherapy can be used to predict hematologic toxicity and customize the current dosing method in radioimmunotherapy.

Estimates of radiation-absorbed dose to kidneys in patients treated with 90Y-ibritumomab tiuxetan.

The aim of the present study was to retrospectively estimate the absorbed dose to kidneys in 17 patients treated in clinical practice with 90Y-ibritumomab tiuxetan for non-Hodgkin's lymphoma, using appropriate dosimetric approaches available. METHODS: The single-view effective point source method, including background subtraction, is used for planar quantification of renal activity. Since the high uptake in the liver affects the activity estimate in the right kidney, the dose to the left kidney serves as a surrogate for the dose to both kidneys. Calculation of absorbed dose is based on the Medical Internal Radiation Dose methodology with adjustment for patient kidney mass. RESULTS: The median dose to kidneys, based on the left kidney only, is 2.1 mGy/MBq (range, 0.92-4.4), whereas a value of 2.5 mGy/MBq (range, 1.5-4.7) is obtained, considering the activity in both kidneys. CONCLUSIONS: Irrespective of the method, doses to kidneys obtained in the present study were about 10 times higher than the median dose of 0.22 mGy/MBq (range, 0.00-0.95) were originally reported from the study leading to Food and Drug Administration approval. Our results are in good agreement with kidney-dose estimates recently reported from high-dose myeloablative therapy with 90Y-ibritumomab tiuxetan.

Expression of substance P and preprotachykinin mRNA by primary sensory neurons in culture: regulation by factors present in peripheral and central target tissues.

Primary sensory neurons display various neuronal phenotypes which may be influenced by factors present in central or peripheral targets. In the case of DRG cells expressing substance P (SP), the influence of peripheral or central targets was tested on the neuronal expression of this neuropeptide. DRG cells were cultured from chick embryo at E6 or E10 (before or after establishment of functional connections with targets). Preprotachykinin mRNA was visualized in DRG cell cultures by either Northern blot or in situ hybridization using an antisense labeled riboprobe, while the neuropeptide SP was detected by immunostaining with a monoclonal antibody. In DRG cell cultures from E10, only 60% of neurons expressed SP. In contrast, DRG cell cultures performed at E6 showed a significant hybridization signal and SP-like immunoreactivity in virtually all the neurons (98%). The addition of extracts from muscle, skin, brain or spinal cord to DRG cells cultured at E6 reduced by 20% the percentage of neurons which express preprotachykinin mRNA and SP-like immunoreactivity. Our results indicate that factors issued from targets inhibit SP-expression by a subset of primary sensory neurons and act on the transcriptional control of preprotachykinin gene.

Site-specific conjugation of a radioiodinated phenethylamine derivative to a monoclonal antibody results in increased radioactivity localization in tumor.

The preparation of a novel radioiodination reagent, the (aminooxy)acetyl derivative of (p-[125]-iodophenyl)ethylamine, is described. Conventional radioiodination of proteins involves the formation of iodotyrosine residues, but for in vivo applications such as thyroid or stomach immunoscintigraphy, the susceptibility of these residues to tissue dehalogenases constitutes a serious disadvantage. Using our new compound, which has a particularly nonreactive aromatic ring, we confirm and extend studies published by other workers indicating the much greater in vivo stability of iodophenyl compounds compared to the more conventional iodophenolic ones. In addition, the aminooxy group of our reagent gives a stable and specific linkage to aldehyde groups formed by periodate oxidation on the sugar moiety of antibody molecules. In vitro, favorable binding activity and high stability was obtained with a (([125I]iodoaryl)amino)oxy labeled monoclonal antibody directed against carcinoembryonic antigen. In vivo, using paired labeling experiments in nude mice bearing colon carcinoma xenografts, the (([125I]iodoaryl)amino)oxy-MAb (MAb = monoclonal antibody) was compared with the same MAb 131I-labeled by conventional chloramine-T method. Tumor 125I concentration of (arylamino)oxy MAb (measured as percent injected dose per gram) was significantly higher as compared to values obtained with a conventionally labeled 131I antibody. Additionally, thyroid uptake, an indicator of iodine release from the antibody, was up to 25 times lower after injection of 125I-MAb obtained by the new method as compared to the conventionally iodinated 131I-MAb.

Calibration of surface contamination monitors for the detection of iodine incorporation in the thyroid gland.

In Switzerland, individuals exposed to the risk of activity intake are required to perform regular monitoring. Monitoring consists in a screening measurement and is meant to be performed using commonly available laboratory instruments. More particularly, iodine intake is measured using a surface contamination monitor. The goal of the present paper is to report the calibration method developed for thyroid screening instruments. It consists of measuring the instrument response to a known activity located in the thyroid gland of a standard neck phantom. One issue of this procedure remains that the iodine radioisotopes have a short half-life. Therefore, the adequacy and limitations to simulate the short-lived radionuclides with so-called mock radionuclides of longer half-life were also evaluated. In light of the results, it has been decided to use only the appropriate iodine sources to perform the calibration.

Polarity of endogenous and exogenous glycosyl-phosphatidylinositol-anchored membrane proteins in Madin-Darby canine kidney cells.

Madin-Darby canine kidney cells (MDCK) were transfected with a cDNA encoding the glycosyl-phosphatidylinositol (GPI)-anchored protein mouse Thy-1 in order to study the steady-state surface distribution of exogenous and endogenous GPI-linked proteins. Immunofluorescence of transfected cells grown on collagen-coated coverslips showed that expression of Thy-1 was variable throughout the epithelium, with some cells expressing large amounts of Thy-1 adjacent to very faintly staining cells. Selective surface iodination of cells grown on collagen-coated or uncoated transwell filters followed by immunoprecipitation of Thy-1 demonstrated that all the Thy-1 was present exclusively in the apical plasma membrane. Although cells grown on uncoated filters had much smaller amounts of Thy-1, it was consistently localized on the apical surfaces. Immunofluorescent localization of Thy-1 on 1 micron frozen sections of filter-grown cells demonstrated that all the Thy-1 was on the apical surface and there was no detectable intracellular pool. Phosphatidylinositol-specific phospholipase C digestion of intact iodinated monolayers released Thy-1 only into the apical medium, indicating that Thy-1 was processed normally in transfected cells and was anchored by a GPI-tail. In agreement with previous findings, endogenous GPI-linked proteins were found only on the apical plasma membrane. These results suggest that there is a common mechanism for sorting and targeting of GPI-linked proteins in polarized epithelial cells.

A novel derivative of the chelon desferrioxamine for site-specific conjugation to antibodies.

We describe the preparation of the modified chelator aminooxyacetyl-ferrioxamine, and the replacement of its iron atom by 67Ga at high specific activity. The aminooxy function of this compound was allowed to react with the aldehyde groups generated by the periodate oxidation of the oligosaccharide of a mouse IgG1 monoclonal antibody (MAb) directed against carcino-embryonic antigen (CEA). The use of the aminooxy group allowed a stable bond to be formed between the chelon and the antibody with no need for reduction. Iron was removed from the ferrioxamine moiety and replaced by 67Ga either before or after conjugation of the chelon to the antibody. In either case the labelled antibody was injected into nude mice bearing a human colon carcinoma having the appropriate antigenicity. Unoxidized antibody, labelled with 125I by conventional methods, was co-injected as an internal control. Additional control experiments were carried out with a non-immune IgG using the same 67Ga-labelled modified chelon as above. The in vivo distribution of the modified antibodies was evaluated at various times between 24 and 96 hr after injection. The methods used were gamma-camera imaging and, more quantitatively, gamma-counting of the various organs after dissection. Interestingly, with the metal-chelon-labelled antibody, the intensity and specificity of tumor labelling was comparable and in some cases superior to the results obtained with radio-iodinated antibody. In particular, there was almost no increase in liver and spleen uptake of radioactive metal relative to radio-iodine, contrary to what has been observed with most antibodies labelled with 111In after conjugation with DTPA.

Groundwater dating and past climate reconstruction

In the past decade aquifers have increasingly become palaeoclimatic archives in their own right alongside ice cores, sediments and other proxy records. The main tool for this task has been the noble gas palaeo-thermometer in combination with quantitative groundwater dating using radionuclides. Noblegas radionuclides play a unique role as tracers in environmental studies due to their chemical inertness and low concentration making them ideal tracers. The same properties on the other hand make them difficult to measure on natural concentration levels. Therefore for decades low level counting (LLC) was the only method for detecting radioisotopes of argon and krypton at an atmospheric level. In recent times and with the increase of interest and potential applications the analytical efforts with novel detection methods have been intensified. In the talk noble gas groundwater dating techniques over times scales from decades to millions of years are discussed in relation to noble gas palaeo records at different locations in Europe and elsewhere.

Phase-I/II radio-immunotherapy study with Iodine-131-labeled anti-CEA monoclonal antibody F6 F(ab')2 in patients with non-resectable liver metastases from colorectal cancer.

Experimental studies in nude mice with human colon-carcinoma grafts demonstrated the therapeutic efficiency of F(ab')2 fragments to carcinoembryonic antigen (CEA) labeled with a high dose of 131Iodine. A phase I/II study was designed to determine the maximum tolerated dose of 131I-labeled F(ab')2 fragments (131I-F(ab')2) from anti-CEA monoclonal antibody F6, its limiting organ toxicity and tumor uptake. Ten patients with non-resectable liver metastases from colorectal cancer (9 detected by CT scan and 1 by laparotomy) were treated with 131I-F(ab')2, doses ranging from 87 mCi to 300 mCi for the first 5 patients, with a constant 300-mCi dose for the last 5 patients. For all the patients, autologous bone marrow was harvested and stored before treatment. Circulating CEA ranged from 2 to 126 ng/ml. No severe adverse events were observed during or immediately following infusion of therapeutic doses. The 9 patients with radiologic evidence of liver metastases showed uptake of 131I-F(ab')2 in the metastases, as observed by single-photon-emission tomography. The only toxicity was hematologic, and no severe aplasia was observed when up to 250 mCi was infused. At the 300-mCi dose, 5 out of 6 patients presented grade-3 or -4 hematologic toxicity, with a nadir for neutrophils and thrombocytes ranging from 25 to 35 days after infusion. In these 5 cases, bone marrow was re-infused. No clinical complications were observed during aplasia. The tumor response could be evaluated in 9 out of 10 patients. One patient showed a partial response of one small liver metastasis (2 cm in diameter) and a stable evolution of the other metastases, 2 patients had stable disease, and 6 showed tumor progression at the time of evaluation (2 or 3 months after injection) by CT scan. This phase-I/II study demonstrated that a dose of 300 mCi of 131I-F(ab')2 from the anti-CEA Mab F6 is well tolerated with bone-marrow rescue, whereas a dose of 200 mCi can be infused without severe bone-marrow toxicity.