Use of the ion exchange method for the determination of stability constants of trivalent metal complexes with humic and fulvic acids—Part I: Eu and Am complexes in weakly acidic conditions

The conditional stability constants for tracer concentrations of Eu(III) and Am(III) with a red earth humic acid (REHA), a red earth fulvic acid (REFA) and a fulvic acid from weathered coal (WFA) were determined at pH 5.2–6.4 (such values are similar to those in non-calcareous soils) in the presence of HAc/NaAc or NaNO₃ by using the cation exchange method. It was found that 1 : 1 complexes were predominately formed in weakly acidic conditions. The total exchangeable proton capacities and the degrees of dissociation of these humic substances were determined by using a potentiometric titration method.

The key parameters necessary for the experimental determination of the conditional stability constants of metal ions with humic substances in weakly acidic conditions by using the cation exchange method were discussed.

The conditional stability constants of 1 : 1 complexes obtained in this paper were compared with the literature data of Am(III) determined by using the ion exchange method and the solvent extraction method and with the stability constants of 1 : 1 complexes of UO₂²⁺ and Th⁴⁺ with the same soil humic substances. These results indicate the great stability of bivalent UO₂²⁺, trivalent Eu³⁺, Am³⁺ and tetravalent Th⁴⁺ complexes with humic and fulvic acids in weakly acidic conditions.     

Rhodium-105 tetrathioether complexes: radiochemistry and initial biological evaluation

ABSTRACT. ¹⁰⁵Rhodium(III) complexes with three different acyclic tetrathioether ligands containing pendant carboxylic acid groups have been synthesized and characterized. The complexes were evaluated for stability under physiological conditions and the most promising complexes were evaluated in vivo in normal mice. The primary route of clearance for these complexes was the renal/urinary system, consistent with the presence of pendant carboxylate groups. The results indicate that the cis-[Rh(III)Cl₂(2,5,8,11-tetrathiadodecane-1,12-dicarboxylic acid)]⁺ complex shows the most promising in vivo characteristics on which to base a potential therapeutic radiopharmaceutical.     

Effect of contrast media on vascular smooth muscle cells

Purpose: In order to alleviate the adverse effects of contrast media (CMs) on the vascular system, the role of Ca²⁺ in the viability of vascular smooth muscle cells (VSMCs) was investigated.

Material and Methods: VSMCs were obtained from swine thoracic aorta. The number of VSMCs was counted under a microscope using the trypan blue dye-exclusion method 24 h after culture in RPMI containing physiological saline (SAL) as control, iothalamate (IOT), or iohexol (IOH) at 10% by volume with CaCl₂ added at 0 to 2.0 mmol/l. Free Ca²⁺ in the above media was measured using an ion-selective electrode.

Results: Free Ca²⁺ was 0.4 to 1.5 mmol/l with ionic IOT and 0.4 to 1.8 mmol/l with non-ionic IOH as well as with control. The ratio of viable cells grown in the presence of CMs to those grown in the control was optimal at approximately 0.60 near 1 mmol/l Ca²⁺ and decreased markedly to 0.00 at 1.5 mmol/l Ca²⁺ in the presence of IOT and to 0.39 at 1.8 mmol/l Ca²⁺ in the presence of IOH, while the ratios decreased gradually to 0.28 in the presence of IOT and 0.53 in the presence of IOH at 0.4 mmol/l Ca²⁺.

Conclusion: Ionic IOT is more cytotoxic to VSMCs than non-ionic IOH. However, the cytotoxicity was minimal and similar between both CMs at 1 mmol/l Ca²⁺ in accordance with the sodium-calcium balance.     

A liquid-scintillation-based primary standardization of Pb

A new radioactivity solution standard of ²¹⁰Pb has been developed and will be disseminated by the National Institute of Standards and Technology (NIST) as standard reference material (SRM) 4337. This new ²¹⁰Pb solution standard is contained in a 5 mL flame-sealed borosilicate glass ampoule, consists of (5.133±0.002) g of a nominal 1 mol L⁻¹ nitric acid solution, has a density of (1.028±0.002) g mL⁻¹ at 20 °C, has carrier ion concentrations of about 11 μg Pb²⁺ and 21 μg Bi³⁺ per gram of solution, and is certified to contain a massic activity (9.037±0.22) kBq g⁻¹ as of the reference time 1200 EST, 15 June 2006. All of the uncertainties cited above correspond to standard uncertainties multiplied by a coverage factor k=2. The standardization for the ²¹⁰Pb content of the solution was based on 4πβ liquid scintillation (LS) measurements using CIEMAT/NIST ³H-standard efficiency tracing (CNET). Confirmatory determinations were also performed by high-resolution HPGe γ-ray spectrometry, by 2π spectrometry with a Si surface barrier detector of separated ²¹⁰Po, and by 4πβ(LS)–γ(NaI) anticoincidence counting.     

Alternative quality control for technetium-99m IDA complexes

A quality control procedure for ^99mTc-IDA complexes based on the use of C₁₈ Sep-pak^TM cartridges is developed and the validation of the procedure presented. C₁₈ Sep-pak^TM cartridges are pretreated by washing with 95% ethanol followed by 10⁻³ N hydrochloric acid. A small amount of the ^99mTc-IDA complex is applied, washed with 10⁻³ N hydrochloric acid and eluted with 95% ethanol. The radiochemical purity values obtained for ^99mTc-mebrofenin and ^99mTc-disofenin using this Sep-pak^TM procedure are comparable to those obtained using the standard two strip (ITLC-SG/100% methanol, ITLC-SA/20% saline) procedure.     

The gallium–deferoxamine complex: stability with different deferoxamine concentrations and incubation conditions

Previous studies report that deferoxamine (DFO) binds metallic ions such as Fe³⁺, In³⁺ and Ga³⁺ with very high affinity. This property of DFO has been utilized to label DFO-coupled compounds with radiometals such as ⁶⁷Ga and ¹¹¹In. We have studied the effect of low DFO concentrations and of different incubation conditions on the stability of the ⁶⁷Ga–DFO complex. In our experience high (>5 μM) DFO concentration appears to be critical in obtaining high radiochemical purity of such complexes.     

Diffusion of Eu(III) in compacted bentonite—effect of pH, solution concentration and humic acid

The effect of pH, Eu(III) solution concentration and humic acid on the diffusion of Eu(III) in compacted bentonite (ρ_b=1000±30 kg/m³) was studied with “in-diffusion” method at an ionic strength of 0.1 M NaClO₄. The results (K_d values from the first slice and theoretical calculation, apparent and effective diffusion coefficients) derived from the new capillary method are in good agreement with the literature data under similar conditions, and fit the Fick's second law very well. The results suggest that the diffusion of Eu(III) is dependent on pH values and independent on solution concentration in our experimental conditions. Humic acid forms precipitation/complexation with Eu(III) at the surface of compacted bentonite and thus deduces the diffusion/transport of Eu(III) in compacted bentonite. The K_d values in compacted bentonite are in most cases lower than those in powdered bentonite obtained from batch experiments. The difference between the K_d values from powdered and compacted bentonite is a strong function of the bulk density of the bentonite. The results suggest that the content of interlaminary space plays a very important role to the diffusion, sorption and migration of Eu(III) in compacted bentonite.     

The behavior of single crystals of NaCl: Ca, Mn exposed to gamma rays

The behavior of single crystals of NaCl: Ca²⁺, Mn²⁺ exposed to gamma rays was explored for its potential usage as a dosimeter. The study was focused to the effect of dose and dose rate. The crystals were analyzed using thermoluminescence (TL). The productions of irradiation defects in the solid were correlated with the glow curve. F-centers were measured as function of the dose. The bleaching of the F-centers produced a decrease of the peak of the glow curve. The results showed that the response is linear in an interval up to 60 Gy.     

In vivo evaluation of copper-64-labeled monooxo-tetraazamacrocyclic ligands

Copper-64 (T_1/2=12.7 h; β⁺: 0.653 MeV, 17.4%; β⁻: 0.578 MeV, 39%) has applications in positron emission tomography (PET) imaging and radiotherapy, and is conveniently produced on a biomedical cyclotron. Tetraazamacrocyclic ligands are the most widely used bifunctional chelators (BFCs) for attaching copper radionuclides to antibodies and peptides due to their relatively high kinetic stability. In this paper, we evaluated three monooxo-tetraazamacrocyclic ligands with different ring sizes and oxo group positions. H1 [1,4,7,10-tetraazacyclotridecan–11-one], H2 [1,4,8,11-tetraazacyclotetradecan-5-one] and H3 [1,4,7,10-tetraazacyclotridecan-2-one] were radiolabeled with ⁶⁴Cu in high radiochemical yields under mild conditions. The three ⁶⁴Cu-labeled complexes are all +1 charged, as determined by their electrophoretic mobility. While they demonstrated >95% stability in rat serum out to 24 h, both biodistribution and microPET imaging studies revealed high uptake and long retention of the compounds in major clearance organs (e.g., blood, liver and kidney), which suggests that ⁶⁴Cu dissociated from the complexes in vivo. Of the three complexes, ⁶⁴Cu-2⁺, which has a cyclam backbone (1,4,8,11-tetraazacyclotetradecane), exhibited the lowest nontarget organ accumulation. The data from these studies may invalidate the candidacy of the monooxo-tetraazamacrocyclics as BFCs for copper radiopharmaceuticals. However, the data presented here suggest that neutral or negatively charged Cu(II) complexes of tetraazamacrocyclic ligands with a cyclam backbone (tetradecane) are optimal for copper radiopharmaceutical applications.     

Sorption and desorption of Eu and Yb on alumina: mechanisms and effect of fulvic acid.

The effects of pH, ionic strength and FA (fulvic acid) on the sorption and desorption of Eu(III) and Yb(III) on alumina were respectively investigated by using batch technique and radiotracers 152 + 154Eu and 169Yb. The distribution coefficients for sorption and desorption of Eu on alumina at pH 4.4, 4.6 and 5.7 in 1 mol/l NaCl solutions as a function of solid phase concentration were determined in the presence or absence of FA. The effects of pH, FA and ionic strength on the distribution coefficients for sorption and desorption of Yb on alumina were determined in 0.01-2.0 mol/l NaNO3. It was found that pH and FA influenced the sorption of Eu(III) and Yb(III) on alumina greatly. A surface hydrolysis model can satisfactorily and qualitatively explain the observations on bare alumina. The competition among the complexations of surface free hydroxyl groups, soluble and sorbed fulvic acids can satisfactorily and qualitatively explain the observations on the coated alumina.     

Effect of pH and concentration on the diffusion of radiostrontium in compacted bentonite—a capillary experimental study

The effects of pH and Sr²⁺ solution concentration on diffusion and sorption of Sr²⁺ in compacted bentonite (ρ_b=1000±30 kg/m³) were studied using an “in-diffusion” method at an ionic strength of 0.1 M NaClO₄. The results (distribution coefficients, K_d, apparent and effective diffusion coefficients, D_a and D_e) derived from the capillary method are in good agreement with the literature data obtained for similar bentonite dry densities and fit Fick's second law very well. The results suggest that the diffusion of Sr²⁺ in compacted bentonite decreases slightly with increasing pH values and also increases slightly with increasing Sr²⁺ solution concentration. The distribution coefficients are weakly dependent on the solution concentrations and show a slight increase with increasing pH values. The average effective diffusion coefficient of Sr²⁺ in compacted bentonite is (1.2±0.2)×10⁻⁹ m²/s, surface diffusion effects are found for the diffusion of Sr²⁺ in compacted bentonite.     

Stabilities of lanthanide-protein complexes

After incubation of both serum and HSA solutions with radioactive lanthanide complexes the binding constants of the corresponding lanthanide-protein complexes formed in the protein solutions under physiologic conditions, pH: 7.4, temperature: 310 K, isotonic ionic strength: 0.15 mol/L, were determined.The association constants of the lanthanide-protein complexes formed both in serum and HSA-solutions are equal within the experimental error. In conclusion, serum albumin binding predominates for the radiolanthanides. With the decrease of the ionic radii from 1.034 Å (Ce) to 0.858 (Yb) the association constants increased by five orders of magnitude from g K_pr = 4.90 (Ce) to 1g K_pr = 9.54 (Yb).Further, a serum fractionation with alcohol was carried out to prove that the albumin fraction of serum is responsible for the lanthanide binding in blood.     

Evaluation of novel cationic 99mTc(I)-tricarbonyl complexes as potential radiotracers for myocardial perfusion imaging

This report describes the evaluation of three cationic ^99mTc(I)–tricarbonyl complexes — [^99mTc(CO)₃(L)]⁺ (L=N-methoxyethyl-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (ME-PNP), N-[15-crown-5)-2-yl]-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (15C5-PNP) and N-[18-crown-6)-2-yl]-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (18C6-PNP)) — as potential radiotracers for myocardial perfusion imaging. Biodistribution, imaging and metabolism studies were performed using Sprague–Dawley rats. It was found that bisphosphine ligands have a significant impact on the biodistribution characteristics and clearance kinetics of their cationic ^99mTc(I)–tricarbonyl complexes. Among the three radiotracers evaluated in this study, [^99mTc(CO)₃(15C5-PNP)]⁺ has a very high initial heart uptake and is retained in the rat myocardium for >2 h. It also shows rapid clearance from the liver and lungs. The heart/liver ratio of [^99mTc(CO)₃(15C5-PNP)]⁺ is 2.5 times better than that of ^99mTc-sestamibi at 30 min postinjection. [^99mTc(CO)₃(15C5-PNP)]⁺ is almost identical to ^99mTcN-DBODC5 with respect to heart uptake, heart/lung ratio and heart/liver ratio. Results from metabolism studies show that there is no significant metabolism for [^99mTc(CO)₃(15C5-PNP)]⁺ in the urine, but it does show a small metabolite peak (<10%) in the radio high-performance liquid chromatography chromatogram of the feces sample at 120 min postinjection. Results planar imaging studies demonstrate that [^99mTc(CO)₃(15C5-PNP)]⁺ has a much better liver clearance profile than ^99mTc-sestamibi and might give clinically useful images of the heart as early as 30 min postinjection. [^99mTc(CO)₃(15C5-PNP)]⁺ is a very promising candidate for more preclinical evaluations in various animal models.     

Postural and respiratory activation of the trunk muscles changes with mode and speed of locomotion

Despite the importance of the deep intrinsic spinal muscles for trunk control, few studies have investigated their activity during human locomotion or how this may change with speed and mode of locomotion. Furthermore, it has not been determined whether the postural and respiratory functions, of which these muscles take part, can be coordinated when locomotor demands are increased. EMG recordings of abdominal and paraspinal muscles were made in seven healthy subjects using fine-wire and surface electrodes. Measurements were also made of respiration and gait parameters. Recordings were made for 10 s as subjects walked on a treadmill at 1 and 2 ms⁻¹ and ran at 2, 3, 4 and 5 ms⁻¹. Unlike the superficial muscles, transversus abdominis was active tonically throughout the gait cycle with all tasks, except running at speeds of 3 ms⁻¹ and greater. All other muscles were recruited in a phasic manner. The relative duration of these bursts of activity was influenced by speed and/or mode of locomotion. Activity of all abdominal muscles, except rectus abdominis (RA), was modulated both for respiration and locomotor-related functions but this activity was affected by the speed and mode of locomotion. This study provides evidence that the deep abdominal muscles are controlled independently of the other trunk muscles. Furthermore, the pattern of recruitment of the trunk muscles and their respiratory and postural coordination is dependent on the speed and mode of locomotion.     

青春期甲状腺功能亢进症对生长发育及精神状态的影响

 目的 探讨青春期甲状腺功能亢进症(甲亢)对生长发育及精神状态的影响。方法 选择2017-01至2018-12武警辽宁总队医院就诊的青春期甲亢患者50例作为观察组,同期随机选择至该院体检的同年龄段青少年50例作为对照组。所有人员均测定身高、体重、甲状腺功能、血清Ca²⁺、P²⁺、ALP,进行PSQI、SAS、SDS问卷调查。比较两组的相关指标,并分析FT₃、FT₄、TSH水平与其他指标的相关性。结果 观察组身高<-2 SD、体重<-2 SD、BMI<18.5(kg/m²)所占比例显著高于对照组,差异有统计学意义(P<0.05)。两组受试者的血清Ca²⁺、P²⁺水平无统计学差异,但观察组ALP水平、PSQI评分、SAS评分、SDS评分均高于对照组,观察组中PSQI≥16分、SAS≥50分、SDS≥53分所占比例亦显著高于对照组,差异有统计学意义(P<0.05)。Pearson相关性分析发现FT₄水平与PSQI评分、SAS评分、SDS评分呈正相关(P<0.05)。结论 青春期甲亢影响青少年的生长发育和精神状态。     

Synthesis and biodistribution of Tc-carbonyltechnetium-labeled fatty acids

In order to image myocardial metabolism, ^99mTc(CO)₃⁺ complexes containing fatty acids were evaluated. At first, 11-(1-imidazolyl)-undecanoic acid (IUA) and 11-(2-(4-bromo-phenylazo)-1-imidazolyl)-undecanoic acid (BPIUA) were synthesized and the corresponding carbonyltechnetium-labeled complexes were prepared. However, unfortunately similar to those of other technetium-labeled fatty acid analogs, the biodistribution studies of ^99mTc(CO)₃–IUA and ^99mTc(CO)₃–BPIUA in mice demonstrated poor heart-to-blood ratios, thus these complexes cannot be used as heart-imaging reagents. In addition, Tween-80 can improve the biodistribution of the complexes for myocardial imaging.     

Radiotracer technique in adsorption study: Part XVII. Removal Behaviour of Alkali Metal (K- and Li-) Titanates for Cd(II)

Alkali metal (potassium and lithium) titanates were synthesized and employed for the efficient removal of Cd(II) ions from aqueous solutions using the radiotracer technique. The possible mechanism involved at the solid/solution interface was deduced with the help of various physico–chemical data, i.e. effect of adsorptive concentration temperature and pH. The effect of added cations and H⁺ (HCl/H₂SO₄) in the uptake process was also seen. The radiation stability of these materials in the adsorption process was assessed by employing a 11.1 GBq (Ra–Be) neutron source having an integral neutron flux of 3.85×10⁶ n·cm⁻² s⁻¹ and associated with a nominal γ-dose of ca. 1.72 Gy/h.     

Stability of biodegradable radioactive rhenium (Re-186 and Re-188) microspheres after neutron-activation

Our objective was to determine if microspheres made from the biodegradable polymer poly(lactic acid) that contained rhenium could withstand the conditions of direct neutron activation necessary to produce therapeutic amounts of radioactive rhenium. The radiation damage of the polymer produced by γ-doses of up to 1.05 MGy from Re-186 and Re-188 was examined by scanning electron microscopy and size exclusion chromatography. At a thermal neutron flux of 1.5×10¹³ n/cm²/s the microspheres melted after 3 h in the nuclear reactor, but suffered little damage after 1 h of radiation and released less than 5% of the radioactivity during incubation in buffer at 37°C. The radioactive microspheres produced in this manner have a specific activity too low for radioembolization for treatment of liver tumors, but could be injected directly into tumors or applied topically to the wound bed of partially resected tumors.     

Paramagnetic complexes of manganese(II), iron(III), and gadolinium(III) as contrast agents for magnetic resonance imaging. The influence of stability constants on the biodistribution of radioactive aminopolycarboxylate complexes

Paramagnetic complexes of manganese(II), iron(III), and gadolinium(III) with many ligands appear to undergo ligand substitution in vivo, producing biodistribution data similar to the hydrated metal ions. To identify ligands likely to be valuable in the preparation of paramagnetic contrast agents, a series of aminopolycarboxylate complexes with stability constants increasing in the order iminodiacetic acid (IDA) less than nitrilotriacetic acid (NTA) less than EDTA less than CDTA less than or equal to DTPA was prepared with 54Mn(II), 59Fe(III), and 153Gd(III) at both tracer and carrier levels. Biodistribution studies in mice suggested that complexes remained unchanged in vivo if their stability constants (K1) were approximately greater than 10(16) for Mn(II) and Gd(III) and greater than 10(22) for Fe(III) complexes at tracer levels. Metal complexes with added carrier appeared to be effectively more stable in vivo, possibly due to dissociation and saturation of metal-binding sites. To avoid the accumulation of metal ions in tissues, new paramagnetic contrast agents containing these metal ions will require stability constants equal to or greater than those identified here.     

Influence of exercise mode and maximal lactate-steady-state concentration on the validity of OBLA to predict maximal lactate-steady-state in active individuals

The aim of this study was to analyze the effects of exercise mode on the validity of onset of blood lactate accumulation (OBLA—3.5-mM fixed blood lactate concentration) to predict the work-rate at maximal lactate steady state (MLSS_work-rate). Eleven recreationally active males (21.3 ± 2.9 years, 72.8 ± 6.7 kg, 1.78 ± 0.1 m) performed randomly incremental tests to determine OBLA (stage duration of 3 min), and 2 to 4 constants work-rate exercise tests to directly determine maximal lactate steady state parameters on a cycle-ergometer and treadmill. For both exercise modes, the OBLA was significantly correlated to MLSS_work-rate, (cycling: r = 0.81 p = 0.002; running: r = 0.94, p < 0.001). OBLA (156.2 ± 41.3 W) was lower than MLSS_work-rate (179.6 ± 26.4 W) during cycling exercise (p = 0.007). However, for running exercise, there was no difference between OBLA (3.2 ± 0.6 m s⁻¹) and MLSS_work-rate (3.1 ± 0.4 m s⁻¹). The difference between OBLA and MLSS_work-rate on the cycle-ergometer (r = 0.86; p < 0.001) and treadmill (r = 0.64; p = 0.048) was significantly related to the specific MLSS. We can conclude that the validity of OBLA on predicting MLSS_work-rate is dependent on exercise mode and that its disagreement is related to individual variations in MLSS.