Using 81Kr and isotopic tracers to characterise old groundwater in the Bangkok metropolitan and vicinity areas.

Krypton-81 was applied to investigate the age of groundwater in the aquifer system in the Bangkok metropolitan and vicinity areas. Stable (2H, 18O and 13C) and radioactive (3H, 85Kr and 14C) isotopes and noble gases were applied in parallel. Low levels of 14C and significant radiogenic 4He confirm that groundwater in the deep aquifers is older than 30 ka. 81Kr analysis identified groundwater with ages ranging from 17 to 300 ka. At some sites, large age discrepancies between 81Kr and 14C indicated that inter-aquifer mixing is likely occurring. The interpretation of the noble gases suggests that groundwaters in the deeper aquifers, with apparent ages of 300 to 10 ka, have recharged in slightly colder and wetter climates than those found in the upper aquifers with apparent ages < 10 ka. Degradation of water quality from seawater intrusion was identified in the upper four aquifers. This was also evidenced by higher δ18O and δ2H values, typical of seawater. The four deeper aquifers contain high quality water characterised by less enriched 18O and 2H. This work presents new findings of very old groundwater in the Bangkok aquifer system.

Developments of a field gas extraction device and krypton purification system for groundwater radio-krypton dating at the IAEA.

The long-lived radio-krypton isotope 81Kr (t1/2 = 2.29 × 105 yr) is an ideal tracer for old groundwater age dating in the range of 105-106 years which goes beyond the reach of radio-carbon (14C) age dating. Analytical breakthrough made over the last two decades in Atom Trap Trace Analysis (ATTA) has enabled the use of this isotope with extremely low abundance (81Kr/Kr = 6 × 10-13) to be used as a practical dating tool for very old groundwater. The International Atomic Energy Agency aims to provide this new isotope tool for better groundwater resource management of Member States and developed a field sampling device to collect dissolved gas samples from groundwater and a system to separate and purify trace amounts of krypton from the gas samples for the ATTA analysis. The design, setup and performances of our sampling and purification systems are described here. Our system can produce a high purity aliquot of about 5 µL of krypton from 5 L of air sample (recovery yield of >90%). The samples made by our system were confirmed to be acceptable for the ATTA analysis.

Proficiency testing of 78 international laboratories measuring tritium in environmental waters by decay counting and mass spectrometry for age dating and water resources assessment.

RATIONALE: Tritium (3 H) is an important hydrological tracer that has been commonly used for over 60 years to evaluate water residence times and water dynamics in shallow/recent groundwaters, streams, lakes and the ocean. We tested the analytical performance of 78 international laboratories engaged in low-level 3 H assays for water age dating and monitoring of environmental waters. METHODS: Seven test waters were distributed by the IAEA to 78 international tritium laboratories. Set 1 included a tritium-free groundwater plus three ultra-low 3 H samples (0.5-7 TU) for meeting groundwater dating specifications. Set 2 contained three higher 3 H-content samples (40-500 TU) suitable for testing of environmental monitoring laboratories. RESULTS: Seventy of the laboratories used liquid scintillation counting with or without electrolytic enrichment, seven utilized 3 He accumulation and mass spectrometry, and one used gas-proportional counting. Only ~50% of laboratories demonstrated the ability to generate accurate 3 H data that was precise enough for water age dating purposes. CONCLUSIONS: The proficiency test helped identify recurrent weaknesses and potential solutions. Strategies for performance improvements of 3 H laboratories include: (a) improved quantification of 3 H detection limits and analytical uncertainty, (b) stricter quality control practices in routine operations along with care and recalibration of 3 H standards traceable to primary NIST standards, (c) annual assessment of tritium enrichment factors and instrumental performance, and (d) for water age dating purposes the use of electrolytic enrichment systems having the highest possible 3 H enrichment factors (e.g. >50×).

Is bone equally responsive to calcium and vitamin D intake from food vs. supplements? Use of (41)calcium tracer kinetic model.

BACKGROUND: Few interventions directly compare equivalent calcium and vitamin D from dairy vs. supplements on the same bone outcomes. The radioisotope calcium-41 ((41)Ca) holds promise as a tracer method to directly measure changes in bone resorption with differing dietary interventions. OBJECTIVE: Using (41)Ca tracer methodology, determine if 4 servings/day of dairy foods results in greater (41)Ca retention than an equivalent amount of calcium and vitamin D from supplements. Secondary objective was to evaluate the time course for the change in (41)Ca retention. METHODS: In this crossover trial, postmenopausal women (n = 12) were dosed orally with 100 nCi of (41)Ca and after a 180 day equilibration period received dairy (4 servings/day of milk or yogurt; ~ 1300 mg calcium, 400 IU cholecalciferol (vitamin D3/day)) or supplement treatments (1200 mg calcium carbonate/day and 400 IU vitamin D3/day) in random order. Treatments lasted 6 weeks separated by a 6 week washout (WO). Calcium was extracted from weekly 24 h urine collections; accelerator mass spectrometry (AMS) was used to determine the (41/40)Ca ratio. Primary outcome was change in (41/40)Ca excretion. Secondary outcome was the time course for change in (41)Ca excretion during intervention and WO periods. RESULTS: The (41/40)Ca ratio decreased significantly over time during both treatments; there was no difference between treatments. Both treatments demonstrated a significant retention of (41)Ca within 1-2 weeks (p = 0.0007 and p < 0.001 for dairy and supplements, respectively). WO demonstrated a significant decrease (p = 0.0024) in (41)Ca retention within 1-2 weeks, back to pre-intervention levels. CONCLUSION: These data demonstrate that urinary (41)Ca retention is increased with an increase in calcium and vitamin D intake regardless of the source of calcium, and the increased retention occurs within 1-2 weeks.

Geostatistical analysis of tritium, groundwater age and other noble gas derived parameters in California.

Key characteristics of California groundwater systems related to aquifer vulnerability, sustainability, recharge locations and mechanisms, and anthropogenic impact on recharge are revealed in a spatial geostatistical analysis of a unique data set of tritium, noble gases and other isotopic analyses unprecedented in size at nearly 4000 samples. The correlation length of key groundwater residence time parameters varies between tens of kilometers ((3)H; age) to the order of a hundred kilometers ((4)Heter; (14)C; (3)Hetrit). The correlation length of parameters related to climate, topography and atmospheric processes is on the order of several hundred kilometers (recharge temperature; δ(18)O). Young groundwater ages that highlight regional recharge areas are located in the eastern San Joaquin Valley, in the southern Santa Clara Valley Basin, in the upper LA basin and along unlined canals carrying Colorado River water, showing that much of the recent recharge in central and southern California is dominated by river recharge and managed aquifer recharge. Modern groundwater is found in wells with the top open intervals below 60 m depth in the southeastern San Joaquin Valley, Santa Clara Valley and Los Angeles basin, as the result of intensive pumping and/or managed aquifer recharge operations.

Ultra-trace analysis of 41Ca in urine by accelerator mass spectrometry: an inter-laboratory comparison.

A 41Ca interlaboratory comparison between Lawrence Livermore National Laboratory (LLNL) and the Purdue Rare Isotope Laboratory (PRIME Lab) has been completed. Analysis of the ratios assayed by accelerator mass spectrometry (AMS) shows that there is no statistically significant difference in the ratios. Further, Bayesian analysis shows that the uncertainties reported by both facilities are correct with the possibility of a slight under-estimation by one laboratory. Finally, the chemistry procedures used by the two facilities to produce CaF2 for the cesium sputter ion source are robust and don't yield any significant differences in the final result.

A membrane inlet mass spectrometry system for noble gases at natural abundances in gas and water samples.

RATIONALE: Noble gases dissolved in groundwater can reveal paleotemperatures, recharge conditions, and precise travel times. The collection and analysis of noble gas samples are cumbersome, involving noble gas purification, cryogenic separation and static mass spectrometry. A quicker and more efficient sample analysis method is required for introduced tracer studies and laboratory experiments. METHODS: A Noble Gas Membrane Inlet Mass Spectrometry (NG-MIMS) system was developed to measure noble gases at natural abundances in gas and water samples. The NG-MIMS system consists of a membrane inlet, a dry-ice water trap, a carbon-dioxide trap, two getters, a gate valve, a turbomolecular pump and a quadrupole mass spectrometer equipped with an electron multiplier. Noble gases isotopes (4)He, (22)Ne, (38)Ar, (84)Kr and (132)Xe are measured every 10 s. RESULTS: The NG-MIMS system can reproduce measurements made on a traditional noble gas mass spectrometer system with precisions of 2%, 8%, 1%, 1% and 3% for He, Ne, Ar, Kr and Xe, respectively. Noble gas concentrations measured in an artificial recharge pond were used to monitor an introduced xenon tracer and to reconstruct temperature variations to within 2 °C. Additional experiments demonstrated the capability to measure noble gases in gas and in water samples, in real time. CONCLUSIONS: The NG-MIMS system is capable of providing analyses sufficiently accurate and precise for introduced noble gas tracers at managed aquifer recharge facilities, groundwater fingerprinting based on excess air and noble gas recharge temperature, and field and laboratory studies investigating ebullition and diffusive exchange.

The management of painful bone metastases with an emphasis on radionuclide therapy.

OBJECTIVE: This review provides an update on the management of painful bone metastases, with an emphasis on radionuclide therapy, and introduces oligometastases and quantitative imaging evaluations for clinical trials. METHODS: The current use of radionuclides, alone and in combination with chemotherapy and radiation therapy for painful bone metastases, is discussed, including toxicity, cost and overall outcomes. RESULTS: Radionuclide therapy is shown to be a useful and cost-effective means of alleviating bone pain in metastatic disease and may be more effective when combined with chemotherapy, bisphosphonates and radiation therapy. Early use of radionuclides in pain therapy may limit cancer progression by inhibiting oligometastases development. Thus, radionuclides can significantly decrease patient morbidity, prolong patient survival, and may decrease the occurrence of new bone metastases. CONCLUSION: Palliative pain therapy is critical for effectively managing bone metastases, with treatment options including analgesics, external beam radiotherapy, chemotherapy and radionuclides. Radionuclide therapy is underutilized. Recent studies using radionuclides with chemotherapy and bisphosponates, or using newer radionuclides or combinations of radionuclides and treatment paradigms (e.g., higher activities, repetitive or cyclic administration, chemo sensitization, chemo supplementation), are encouraging. A comprehensive, inter-disciplinary clinical approach is needed. Clinical collaborations will optimize radionuclide therapy for pain palliation and increase awareness of its benefits.

Evaluation of 41calcium as a new approach to assess changes in bone metabolism: effect of a bisphosphonate intervention in postmenopausal women with low bone mass.

UNLABELLED: A new technique was evaluated to identify changes in bone metabolism directly at high sensitivity through isotopic labeling of bone Ca. Six women with low BMD were labeled with 41Ca up to 700 days and treated for 6 mo with risedronate. Effect of treatment on bone could be identified using 41Ca after 4-8 wk in each individual. INTRODUCTION: Isotopic labeling of bone using 41Ca, a long-living radiotracer, has been proposed as an alternative approach for measuring changes in bone metabolism to overcome current limitations of available techniques. After isotopic labeling of bone, changes in urinary 41Ca excretion reflect changes in bone Ca balance. The aim of this study was to validate this new technique against established measures. Changes in bone Ca balance were induced by giving a bisphosphonate. MATERIALS AND METHODS: Six postmenopausal women with diagnosed osteopenia/osteoporosis received a single oral dose of 100 nCi 41Ca for skeleton labeling. Urinary 41Ca/40Ca isotope ratios were monitored by accelerator mass spectrometry up to 700 days after the labeling process. Subjects received 35 mg risedronate per week for 6 mo. Effect of treatment was monitored using the 41Ca signal in urine and parallel measurements of BMD by DXA and biochemical markers of bone metabolism in urine and blood. RESULTS: Positive response to treatment was confirmed by BMD measurements, which increased for spine by +3.0% (p = 0.01) but not for hip. Bone formation markers decreased by -36% for bone alkaline phosphatase (BALP; p = 0.002) and -59% for procollagen type I propeptides (PINP; p = 0.001). Urinary deoxypyridinoline (DPD) and pyridinoline (PYD) were reduced by -21% (p = 0.019) and -23% (p = 0.009), respectively, whereas serum and urinary carboxy-terminal teleopeptides (CTXs) were reduced by -60% (p = 0.001) and -57.0% (p = 0.001), respectively. Changes in urinary 41Ca excretion paralleled findings for conventional techniques. The urinary 41Ca/40Ca isotope ratio was shifted by -47 +/- 10% by the intervention. Population pharmacokinetic analysis (NONMEM) of the 41Ca data using a linear three-compartment model showed that bisphosphonate treatment reduced Ca transfer rates between the slowly exchanging compartment (bone) and the intermediate fast exchanging compartment by 56% (95% CI: 45-58%). CONCLUSIONS: Isotopic labeling of bone using 41Ca can facilitate human trials in bone research by shortening of intervention periods, lowering subject numbers, and having easier conduct of cross-over studies compared with conventional techniques.

The bisphosphonate olpadronate inhibits skeletal prostate cancer progression in a green fluorescent protein nude mouse model.

PURPOSE: Metastatic bone disease is one of the major causes of morbidity and mortality in prostate cancer patients. Bisphosphonates are currently used to inhibit bone resorption and reduce tumor-induced skeletal complications. More effective bisphosphonates would enhance their clinical value. EXPERIMENTAL DESIGN: We tested several bisphosphonates in a green fluorescent protein (GFP)-expressing human prostate cancer nude mouse model. The in vivo effects of four bisphosphonates, including pamidronate, etidronic acid, and olpadronate, on bone tumor burden in mice intratibially inoculated with PC-3-GFP human prostate cancer cells were visualized by whole-body fluorescence imaging and X-ray. RESULTS: The PC-3-GFP cells produced extensive bone lesions when injected into the tibia of immunocompromised mice. The skeletal progression of the PC-3-GFP cell growth was monitored by GFP fluorescence and the bone destruction was evaluated by X-ray. We showed that 3,3-dimethylaminopropane-1-hydroxy-1,1-diphosphonic acid (olpadronate) was the most effective bisphosphonate treatment in reducing tumor burden as assessed by GFP imaging and radiography. The GFP tumor area and X-ray score significantly correlated. Reduced tumor growth in the bone was accompanied by reduced serum calcium, parathyroid hormone-related protein, and osteoprotegerin. CONCLUSIONS: The serum calcium, parathyroid hormone-related protein, and osteoprotegerin levels were significantly correlated with GFP area and X-ray scores. Treatment with olpadronate reduced tumor growth in the bone measured by GFP and X-ray imaging procedures. Imaging of GFP expression enables monitoring of tumor growth in the bone and the GFP results complement the X-ray assessment of bone disease. The data in this report suggest that olpadronate has potential as an effective inhibitor of the skeletal progression of clinical prostate cancer.

41Ca and accelerator mass spectrometry to monitor calcium metabolism in end stage renal disease patients.

BACKGROUND: Monitoring bone resorption with measurements of bone density and biochemical markers is indirect. We hypothesized that bone resorption can be studied directly by serial measurements of the ratio (41)Ca/Ca in serum after in vivo labeling of calcium pools with (41)Ca. We report the preparation of an intravenous (41)Ca dose suitable for humans, an analytical method for determining (41)Ca/Ca isotope ratios in biological samples, and studies in human volunteers. METHODS: (41)Ca was formulated and aliquoted into individual vials, and to the extent possible, the (41)Ca doses were tested according to US Pharmacopeia (USP) guidelines. A 10 nCi dose of (41)Ca was administered intravenously to 4 end stage renal disease (ESRD) patients on hemodialysis and 4 healthy control individuals. Distribution kinetics were determined over 168 days. Calcium was isolated with 3 precipitation steps and a cation-exchange column, and (41)Ca/Ca ratios in serum were then measured by accelerator mass spectrometry. RESULTS: The dosing solution was chemically and radiologically pure, contained <0.1 endotoxin unit/mL, and passed USP sterility tests. Quantification of (41)Ca/Ca ratios was linear from 6 x 10(-14) to 9.1 x 10(-10). The run-to-run imprecision (as CV) of the method was 4% at 4.6 x 10(-11) and 6% at 9.1 x 10(-10). The area under the curve of (41)Ca in the central compartment vs time was significantly less for ESRD patients than for controls (P < 0.005). CONCLUSIONS: Isotope ratios spanning 5 orders of magnitude can be measured by accelerator mass spectrometry with excellent precision in the range observed in samples collected from patients who have received 10 nCi of (41)Ca. The (41)Ca at this dose caused no adverse effects in 8 volunteers. This is the first report of the use of (41)Ca to monitor differences in bone turnover between healthy individuals and ESRD patients.

Neuroscience and accelerator mass spectrometry.

Accelerator mass spectrometry (AMS) is a mass spectrometric method for quantifying rare isotopes. It has had a great impact in geochronology and archaeology and is now being applied in biomedicine. AMS measures radioisotopes such as 3H, 14C, 26Al, 36Cl and 41Ca, with zepto- or attomole sensitivity and high precision and throughput, allowing safe human pharmacokinetic studies involving microgram doses, agents having low bioavailability or toxicology studies where administered doses must be kept low (<1 microg kg(-1)). It is used to study long-term pharmacokinetics, to identify biomolecular interactions, to determine chronic and low-dose effects or molecular targets of neurotoxic substances, to quantify transport across the blood-brain barrier and to resolve molecular turnover rates in the human brain on the time-scale of decades. We review here how AMS is applied in neurotoxicology and neuroscience.

Alpha-particle energy loss measurement of microgram depositions of biomolecules.

A commercially available alpha-particle spectrometer and 210Po alpha-particle source were used to determine the mass of microgram quantities of biomolecules. Samples were deposited in microliter volumes on thin silicon nitride windows and dried. The energy loss of the alpha-particles after traversing the sample was converted to a mass using tabulated alpha-particle stopping powers. The measurement was absolute, independent of biomolecule species, and no standards were needed for quantitation. The method has a dynamic range of 0.1-100 microg for deposits of diameter 1-2 mm. The precision varies from approximately 20% at 100 ng to a few percent at 5-100 microg. The silicon nitride windows allow multimodal analysis of the same quantified sample, including PIXE probing of elemental abundances, molecular identification by mass spectrometry, and isotopic quantitation of interactions. The method was used with accelerator mass spectrometry to quantify specific activities of microgram quantities of 14C-labeled proteins.