Chemical and isotopic characterization of the thermal fluids emerging along the North-Northeastern Greece.

Hydrochemical and isotopic characteristics of fluids from major geothermal fields of middle/low temperature in N/NE Greece are examined [basins: Strymon River (SR), Nestos River Delta (ND), Xanthi-Komotini (XK), Loutros-Feres-Soufli (LFS) and Rhodope Massif]. The geodynamic context is reflected to isotopic/chemical composition of fluids, heat flow values and elevated CO2 concentrations in emitted fluids. B and Li are derived from leaching of the geothermal systems hosting rocks. δ18OH2O, δ18OSO4, δ13CCO2 values and chemical compositions of Cl, B and Li of geothermal discharges suggest two distinct source fluids. Fluids in SR exhibit high B/Cl and Li/Cl ratios, suggesting these constituents are derived from associated magmas of intermediate composition (andesitic rocks). Geothermal discharges in LFS exhibit low B/Cl and Li/Cl ratios, implying acid (rhyolitic) magmatism. δ13CCO2 and CO2/(CO2 + 105He) ratios in the west part, suggest fluids affected by addition of volatiles released from subducted marine sediments. For the eastern systems, these ratios suggest gas encountered in systems issued from mixing of crustal and mantle-derived volatiles. Isotopic geothermometers reflect, for the same direction, equilibrium processes more (LFS, XK) or less (SR) pronounced and discriminate the geothermal field from low to middle [SR, ND (Erasmio)] and middle to high enthalpy [ND (Eratino), LFS, XK].

Urbanization impact on sulfur content of groundwater revealed by the study of urban speleothem-like deposits: Case study in Paris, France.

Speleothem-like deposits that develop underground in urban areas are an archive of the environmental impact of anthropic activities that has been little studied so far. In this paper, the sulfate content in shallow groundwater from northern Paris (France) is compared with the sulfur content in two 300-year-old urban carbonate deposits that grew in a historical underground aqueduct. The present-day waters of the aqueduct have very high sulfur and calcium contents, suggesting pollution from gypsum dissolution. However, geological gypsum levels are located below the water table. Sulfur content was measured by micro-X-ray fluorescence in these very S-rich carbonate deposits (0.5 to 1% of S). A twofold S increase during the second half of the 1800s was found in both samples. These dates correspond to two major periods of urbanization above the site. We discus three possible S sources: anthropic sources (industries, fertilizers…), volcanic eruptions and input within the water through gypsum brought for urbanization above the studied site (backfill with quarry waste) since the middle of the 19th century. For the younger second half of the studied section, S input from gypsum brought during urbanization was confirmed by the study of isotopic sulfur composition (δ34S=+15.2‰ at the top). For the oldest part, several sulfur peaks could be related to early industrial activity in Paris, that caused high local air pollution, as reported in historical archives but also to historical gypsum extraction. This study provides information on the origin and timing of the very high SO42- levels measured nowadays within the shallow groundwater, thus demonstrating the interest in using carbonate deposits in urban areas as a proxy for the history of urbanization or human activities and their impact on water bodies.

Comparative study of Se oxyanions retention on three argillaceous rocks: Upper Toarcian (Tournemire, France), Black Shales (Tournemire, France) and Opalinus Clay (Mont Terri, Switzerland).

A comparative study of selenium oxyanion sorption was carried out by means of batch sorption experiments on three argillaceous rocks that differ in their mineralogical compositions and textural properties. The results show no selenate (Se(VI)) sorption onto the argillaceous rocks after 60 days, but clear sorption of selenite (Se(IV)), the extent being closely related to the initial Se(IV) concentration. At the lowest concentration ([Se(IV)]eq < 10(-8) mol L(-1)), the ranking of rock affinity for Se(IV) is Black Shales > Opalinus Clay (OPA) > Upper Toarcian, with Rd values of 910 ± 70, 600 ± 65 and 470 ± 70 mL g(-1) respectively. The Se(IV) sorption isotherms acquired for the three argillaceous rocks can be reproduced well by means of Langmuir formalism, particularly with a two-site Langmuir model. The comparison of the Se(IV) sorption isotherms obtained for these three rocks led to identification of pyrite associated with natural organic matter (NOM) as one of the main phases involved in selenium retention. While the desorption results suggested a significant Se(IV) reduction in the Upper Toarcian samples, the reversible sorption shown on the Black Shales and OPA samples was correlated with a sulfate increase, symptomatic of surface oxidation of pyrite which could limit the Se(IV) reduction in favor of sorption.

A laboratory experiment for determining both the hydraulic and diffusive properties and the initial pore-water composition of an argillaceous rock sample: a test with the Opalinus clay (Mont Terri, Switzerland).

Argillaceous formations are thought to be suitable natural barriers to the release of radionuclides from a radioactive waste repository. However, the safety assessment of a waste repository hosted by an argillaceous rock requires knowledge of several properties of the host rock such as the hydraulic conductivity, diffusion properties and the pore water composition. This paper presents an experimental design that allows the determination of these three types of parameters on the same cylindrical rock sample. The reliability of this method was evaluated using a core sample from a well-investigated indurated argillaceous formation, the Opalinus Clay from the Mont Terri Underground Research Laboratory (URL) (Switzerland). In this test, deuterium- and oxygen-18-depleted water, bromide and caesium were injected as tracer pulses in a reservoir drilled in the centre of a cylindrical core sample. The evolution of these tracers was monitored by means of samplers included in a circulation circuit for a period of 204 days. Then, a hydraulic test (pulse-test type) was performed. Finally, the core sample was dismantled and analysed to determine tracer profiles. Diffusion parameters determined for the four tracers are consistent with those previously obtained from laboratory through-diffusion and in-situ diffusion experiments. The reconstructed initial pore-water composition (chloride and water stable-isotope concentrations) was also consistent with those previously reported. In addition, the hydraulic test led to an estimate of hydraulic conductivity in good agreement with that obtained from in-situ tests.

Isotopes and groundwater management strategies under semi-arid area: case of the Souss upstream basin (Morocco).

This study concerns the Souss upstream basin. The objective is to investigate the characteristics of surface water and groundwater, to assess the impact of artificial recharge as reinforcement of the natural replenishment and assess the renewal of groundwater under semi-arid area. Two major water types are observed: (i) surface waters and upstream springs (least mineralized) and (ii) all groundwater samples (prevailing calcium and magnesium bicarbonate water type). Water isotopes show a low evaporation of precipitations during infiltration. Impoverishment in heavy isotopes is the characteristic of mountain rainfalls, or of a climate colder and wetter than present. Carbon-14 activities (34-94 pmc) indicate a long residence time. The artificial recharge is low compared to the reservoir volume, due to which the renewal rate is also low.

Synthesis, characterization and comparative biodistribution study of a new series of p-iodine-125 benzamides as potential melanoma imaging agents.

Iodobenzamides are reported to possess some affinity for melanoma. In order to identify the compound having the most appropriate pharmacokinetic properties as a potential melanoma imaging agent, thirteen new [125I]radioiodobenzamides with a butylene amide-amine spacer and various substituents on the terminal amino group were investigated. Their synthesis, radioiodination and biodistribution in B16 melanoma bearing C57BL6 mice are described and compared to [125I] labeled N-(2-diethylaminoethyl)-4-iodobenzamide ([125I]BZA), our reference compound. Changes in the terminal amino constituents induced modifications of lipophilicity, tumor uptake and organ distribution. The dimethylaminobutyl iodobenzamide appeared to be the most promising radiopharmaceutical imaging agent for the detection of melanoma and its metastases.

Distribution of I-BZA (N-2-diethylaminoethyl-4-iodobenzamide) in grafted melanoma and normal skin: a study by secondary ion mass spectroscopy.

Iodobenzamides labelled with radioactive iodine are undergoing clinical evaluation as imaging and potential therapeutic agents in malignant melanomas. However, the uptake mechanism in melanic tissues remains controversial. Using secondary ion mass spectrometry (SIMS), we studied the microscopic distribution of N-(2 diethylaminoethyl)-4 iodobenzamide (I-BZA) in B16 murine melanoma inoculated to C57BL/6J1 Co mice as well as in normal pigmented skin. SIMS provides specific detection of iodine-127 atoms entering 127I-BZA composition. In B16 melanoma, 127I-BZA distribution was found to be heterogeneous, with focal areas of high concentration corresponding to cells rich in melanin pigments. In skin, SIMS analysis showed 127I-BZA distribution appearing as multiple small selective concentration areas within the epidermis. The number of these foci decreased from the stratum basale towards the stratum corneum. In both tissues, the intracellular location appeared specifically intracytoplasmic, with no apparent nuclear uptake. Distribution of this molecule mirrored that of melanin pigments. There was no enhancement of uptake at the membrane site. These results suggest that, in melanic tumors as well as in normal pigmented tissue, specific uptake of 127I-BZA occurs in pigment cells, with a possible link to melanin pigments.

Establishment of IPC 227 cells as human xenografts in rabbits: a model of uveal melanoma.

This study was designed in order to evaluate the feasibility of establishing an animal model of human uveal melanoma. IPC227, a cell line established from the biopsy of a patient with a spindle cell ciliary body melanoma, was transplanted into the anterior chamber of the eye in immunosuppressed New Zealand rabbits. In a second step, a tumour fragment from the anterior chamber was implanted transclerally into the posterior choroid. Complete ophthalmological examinations were then performed on the animals. Characteristic growth patterns were noted depending on the location of implantation. In the anterior chamber, diffuse, flat, heavily pigmented tumours appeared 8 days after the injection of the cell suspension that covered the iris and the angle by day 25, with a success rate of 100%. Nodular, lightly pigmented tumours were obtained 6-7 weeks after subchoroidal implantation, with a 25% success rate. Clinical examination, including fundus photography, ultrasound and magnetic resonance imaging, demonstrated the same characteristics as those of human uveal melanoma, confirming the value of this model for the evaluation of new therapeutic and diagnostic methods in the management of uveal melanoma.

Clinical study of [123I] N-(2-diethylaminoethyl)-4-iodobenzamide in the diagnosis of primary and metastatic ocular melanoma.

PURPOSE: To assess the value of scintigraphy with [123I]N-(2-diethylaminoethyl)-4-iodobenzamide (BZA), a phase II clinical trial was performed on 48 patients with a suspicion of ocular melanoma. METHODS: 56 examinations were performed to image lesions with a clinical diagnosis of primary ocular melanoma before and/or after treatment, to observe the results in simulating lesions or to image metastases. RESULTS: Ocular BZA-scintigraphy demonstrated a sensitivity of 86%, and a specificity of 83%. Whole-body scintigraphy was used in the follow-up of treated patients and could be repeated. We imaged orbital recurrence, known and occult metastases, specially in the liver. After 9 conservative treatments ocular BZA-scintigraphy was negative in 9 eyes. CONCLUSION: The BZA-scintigraphy in combination with other diagnostic procedures appeared to be a suitable method in the diagnosis of ocular melanoma and a potentially useful imaging modality to screen for ocular malignant melanoma metastases.

Application of textural features to the detection of ocular melanomas in scintigraphy.

A method for automated detection of ocular melanoma in scintigraphic images is described. The algorithm first performs an automatic segmentation of the eyes on specific reference images. The images of the eyes are then analyzed using textural parameters computed in several directions and averaged to damp directional information. Assuming that only one eye per patient will be pathological, the ratio of the textural parameters of the two eyes is computed. A statistical analysis is performed over these ratios to select the most highly discriminating textural parameters and detect the pathological patients. The method has been tested successfully on a population of 23 individuals and we found significant differences between pathological and normal patients.

Localization of N-(2-diethylaminoethyl)4-iodobenzamide in the pigmented mouse eye: a microanalytical study.

The 123I-N-(2-diethylaminoethyl)4-iodobenzamide (123I-BZA) is a new radiopharmaceutical used for the scintigraphic imaging of malignant melanomas. The mechanism for BZA uptake in melanic tissues is still unknown. Two methods of microanalysis, secondary ion mass spectrometry and electron probe X-ray microanalysis, were used to determine tissue distribution and subcellular location of unlabelled BZA in the C57BL6/J1 co mouse eye. Microanalysis showed elective BZA uptake by the pigmented structures of the eye: choroidal melanocytes and retinal pigment cells, where it was specifically located within melanosomes. The tropism of BZA for melanic tumours, as well as for normal pigmented tissues, could be explained by a high affinity for the melanin pigment.

Synthesis, radiolabeling, and preliminary evaluation in mice of some (N-diethylaminoethyl)-4-iodobenzamide derivatives as melanoma imaging agents.

N-(2-Diethylaminoethyl)-4-iodobenzamide (BZA) is a radiopharmaceutical recently developed in our laboratory for the scintigraphic detection of melanoma and metastases. Optimal time for imaging was between 18-24 h p.i. of [123I] BZA. With a view to selecting compounds able to provide quality images shortly after the injection, synthesis of an initial series of BZA derivatives and their evaluation in B16 melanoma bearing mice have been carried out. The [125I] radiolabeled products were obtained by a simple isotopic exchange procedure with high radiochemical yields (85-95%). After i.v. administration of the compounds we observed a good tumoral targeting ability. Tumoral activity peaked at 2.6 to 7.70% injected dose per g within 1 h post-injection. One of the benzamides with a blood clearance faster than that of BZA--0.06 vs. 0.2% I D/g--6 h p.i. gave the same tumor to blood and to organ ratios as BZA at 12-18 h p.i. Based on these preclinical data we hope to obtain good tumoral images 6 h p.i. in scintigraphic studies in man.

A radiolabelled iodobenzamide for malignant melanoma staging.

123I-N-(di-ethylamino-2-ethyl) 4 iodobenzamide (I-BZA) has been put forward by the Clermont-Ferrand INSERM U71 group (France) as a tracer for malignant melanoma. We report on the clinical results obtained in 56 studies performed on 48 patients. Whole body scans along with spot views were obtained after injection of 185 MBq of I-BZA. The scans were read by three independent observers and correlated to the clinical findings and the other imaging modalities available, taking into account all lesions larger than 1 cm. Patients were classified into two groups on the basis of a post-treatment survey of patients: group I, in complete remission (24 scans); group II: documented metastases (32 scans). In group 1, 21 studies were truly negative. However, three studies showed positive results. Only one turned out to be a false positive (specificity 95%), the other two revealed unknown lesions and modified the patients' management. In group II, 73% of the known metastases were detected with higher sensitivities (> 80%) for eye and orbit, lung and abdomen. One false positive was reported and four new lesions were detected. I-BZA scintigraphy has the same sensitivity as immunoscintigraphy with higher specificity and without the risk of xenoimmunization. It is a useful tool for staging malignant melanoma which can improve patient management.

In vitro uptake of technetium-99m-teboroxime in carcinoma cell lines and normal cells: comparison with technetium-99m-sestamibi and thallium-201.

Since 201Tl, 99mTc-sestamibi and 99mTc-teboroxime concentrate in cardiac cells through different mechanisms, we compared their uptake in cultured normal cells and carcinoma cell lines in order to define their possible use for tumor evaluation in vivo. Four lines of normal cells from animals, including myocytes from newborn rats, and four lines of human carcinoma cell lines were incubated for 1 hr with 37 kBq of either tracer. Results, expressed in percent of the total activity taken up by 1 million cells, showed a 9% difference between the uptake of teboroxime by normal and carcinoma lines (24.6% +/- 2.8% versus 22.5% +/- 2.1%, respectively, p < 0.05). Mean uptake was 80% higher in tumor than in normal cells for 201Tl (5.39% +/- 1.33% versus 3.00% +/- 1.08%, respectively, p < 0.001) and nearly 4 times higher for sestamibi (5.37% +/- 2.34% versus 1.44% +/- 1.88%, p < 0.001). For both agents, uptake by the myocytes and carcinoma cells was comparable (5.14% +/- 0.11% for 201Tl and 5.28% +/- 1.03% for sestamibi). When the myocytes are excluded from the group of normal cells, the uptake is 112% higher in tumor than in normal cells for 201Tl (5.39% +/- 1.33% versus 2.54% +/- 0.44%, p < 0.001) but it becomes nearly nine times higher for sestamibi (5.37% +/- 2.34% versus 0.60% +/- 0.23%, p < 0.001). It is concluded that these experiments show that the uptake of sestamibi was the most discriminant to separate between normal and malignant cells, while teboroxime was the less discriminant. Potential clinical applications for tumor visualization based on differences in sestamibi and teboroxime uptake could be envisioned.

Phase II scintigraphic clinical trial of malignant melanoma and metastases with iodine-123-N-(2-diethylaminoethyl 4-iodobenzamide).

Preclinical studies established [125I]-N-(2-diethylaminoethyl) 4-iodobenzamide (BZA) as a potential radiopharmaceutical in the management of patients with malignant melanoma. External detection of both murine and human melanotic melanomas was possible after intravenous injection of 125I-BZA in tumor-bearing mice. This article reports a Phase II clinical trial evaluating 123I-BZA as an imaging agent of primary melanomas and metastases. A total of 110 patients with a history of melanoma were investigated in two nuclear medicine departments. Subjects were imaged from 20 to 24 hr after the intravenous injection of 3.5 mCi (130 MBq) of 123I-BZA. After injection, no short-term or long-term side effects were noted. Calculated on a lesion-site basis, diagnostic sensitivity was 81%, accuracy was 87% and specificity was 100%. The melanoma nature of previously occult lesions was confirmed by clinical criteria and/or additional investigations in follow-up studies. The scintigraphies were normal in 44 patients in clinical remission after treatment of malignant melanoma and in seven patients with nonmelanoma disease. No false positive results were observed. Iodine-123-BZA scintigraphy appears to be a safe and useful agent for the detection and follow-up of patients with malignant melanoma. BZA also allowed the detection of unsuspected lesions and the evaluation of the results of various therapeutic procedures such as surgery, chemotherapy, immunobiology, biological therapy or radiotherapy.

Synthesis and evaluation of new iodine-125 radiopharmaceuticals as potential tracers for malignant melanoma.

The synthesis, labeling, and biodistribution of four 125I radiopharmaceuticals designed to localize in melanoma were tested. Uptake in tumors was demonstrated by autoradiography of whole-body sections and quantitated by measurement of radioactivity of selected tissues and tumors using melanoma-bearing mice. N-(2-diethylaminoethyl)-4-iodobenzamide was selected for its highest melanoma uptake: 60 min after IV injection of 6.5% and 4% ID/g, respectively for murine B16 and human melanotic melanoma. Tumor uptake showed the highest values of all analyzed tissues from 6 to 24 hr after injection. High uptake in melanotic tumor tissue with relatively low uptake in blood, muscle, brain, lung, and liver tissue resulted in high tumor/nontumor ratios (at 24 hr for B16, tumor/blood = 37, tumor/brain = 147, tumor/muscle = 95). This agent was compared with iodoamphetamine. Scintigraphic images of the tumor confirmed that external detection of melanoma is possible with this new radiopharmaceutical.

[Perspectives of scintigraphic diagnosis of malignant lymphoma using a new radiopharmaceutical]. / Perspectives de diagnostic scintigraphique du mélanome malin par un nouveau radiopharmaceutique.

In the sequence of our studies on radiopharmaceuticals for malignant melanoma detection the results were most promising for the possible use of 125I or 123I-N-(2-diethyl amino ethyl)4-iodobenzamide. The biodistribution in mice bearing melanoma either human or animal from 4 to 24 hrs. post i.v. injection showed high uptake in tumor tissue together with relatively low uptake in muscle, brain, lung and liver. Scintigraphic images of the tumor obtained at the same times confirmed that melanoma detection was very promising.

Brain uptake of labelled adiphenine in rats.

This study describes the behaviour of a dual labelled drug, adiphenine, in the rat brain. Macroautoradiographies show images of the brain at different times after injection. Some of the tissue metabolites are identified at the brain level and the passage of the blood brain barrier is compared with tritiated water. The obtained data give very interesting indications on the blood brain distribution and on the metabolism at the brain level. Different techniques of high pressure liquid chromatography, macro- and histoautoradiographies allowed us to visualize how the drug is fixed on cerebral structures, giving indications on its mechanism of action. This fat soluble compound freely crosses the normal blood brain barrier and if labelled with the appropriate emittor could be very useful in nuclear medicine to obtain imaging of the brain.

Adiphenine plasma levels and blood-brain barrier crossing in the rat.

Adiphenine was administered in 3H-labelled form in doses of 15 mumole/kg intravenously to male Wistar rats. Plasma and brain levels of the unchanged drug were measured. The elimination of the 3H-labelled compound from the plasma was monophasic with a half-life of 13 minutes. The unchanged drug was detectable in the plasma for 30 minutes after the injection. The time course of brain levels of unchanged drug paralleled that found in the plasma with a half-life of 9 to 12 minutes. In all experiments, brain and plasma levels of unchanged adiphenine correlate highly.

IgG purification to measure the level of an iodinated thyroglobulin peptide, the 3,5,3',5' tetraiodo-l-tyrosyl-l-tyrosine in human serum.

Antibodies reacting with 3,5,3',5' tetraiodo-l-tyrosyl-l-tyrosine (I2Tyr-I2Tyr) were elicited in rabbits by immunization with an oxidized yeast conjugate coupled with I2Tyr-I2Tyr. Ion-exchange chromatography was used to purify immunoglobulins, in order to improve the specificity in measurement of I2Tyr-I2Tyr level in patient serum. IgG binding capacity versus I2Tyr-I2Tyr was considerably increased after immunoglobulin purification.