Effects of mercapto-palygorskite application on cadmium accumulation of soil aggregates at different depths in Cd-contaminated alkaline farmland.

Mercapto-palygorskite (MP) is a novel immobilization material for cadmium (Cd) pollution, but the immobilization mechanism on alkaline Cd contaminated soil is not completely clear. In this paper, field experiment was carried out to study the effect of MP on the transfer of Cd in aggregates at different depth, the contribution of soil aggregates to the reduction of Cd in bulk soil and the immobilization mechanism of MP. The results showed that MP had no significant influence on the total Cd content, soil aggregates distribution, pH value, CEC value and enzyme activities no matter at any depth. At the depth of 0-20 cm, MP significantly reduced the DTPA-Cd in bulk soil by 60.7%, and increased the GWD and R0.25 value. Similarly, the content of DTPA-Cd in the soil aggregates was deceased by 40.2-63.6%, the OM, DOC, available Fe, Mn and S in soil aggregates were significantly increased by 15.0-19.1%, 19.2-41.7%, 24.7-41.2% and 12.5-35.1% respectively. The Cd fraction of aggregates, especially exchangeable Cd (EXE-Cd) and bound to Fe/Mn oxide Cd (OX-Cd), was reduced by 5.4-28.1% and increased by 22.3-50.4%. In addition, MP had different effects on the GSF value of soil aggregates, but there was a downward trend for AFX value at 0-20 cm soil depth. MP almost had no significant influence on the above indexes at the depth of 20-40 cm and 40-60 cm, but except the Cd fraction, the GSF and AFX value in individual aggregates. Small aggregates (<1 mm) and large aggregates (>1 mm) contributed 59.1% and 22% to the reduction of Cd in bulk soil. Partial Least Structural Equation Model (PL-SEM) revealed that S promoted the production of available Fe, Mn, OM and DOC, while the content of DOC inhibited the formation of EXE-Cd and the available Fe and Mn boosted the production of OX-Cd.

Optimum Olsen Phosphorus/ZincDTPA ratio for the initial growth of maize in agricultural soils of the Mediterranean region.

BACKGROUND: Zinc (Zn) deficiency in crops is commonly aggravated by high levels of phosphorus (P) in soil. In this work, the initial performance of pot-growing maize in response to the available P and Zn in soils with low available Zn and to the application of P and Zn fertilizers was investigated. RESULTS: The soils (six non-calcareous and 14 calcareous) ranged widely in available P (Olsen P: 5.5-37.9 mg kg-1 ), were poor in available Zn [diethylenetriaminepentaacetic acid-extractable Zn (ZnDTPA ): 0.20-0.84 mg kg-1 ] and had an Olsen P/ZnDTPA ratio of 13 to 111 mg mg-1 . Soil P application generally increased aerial dry matter (ADM) yield; Zn increased ADM yield mostly when applied in combination with P; and the sole application of Zn increased yield only in a soil with a high (28 mg kg-1 ) Olsen P and a low (0.36 mg kg-1 ) ZnDTPA . The increase in ADM yield resulting from optimal application of P and/or Zn to the soil was modest in soils where the Olsen P/ZnDTPA ratio was 30-60 and Olsen P was >14 mg kg-1 . Zinc uptake by the control plants was correlated with the ZnDTPA of the soil. For a certain ZnDTPA value, the level of plant available Zn was higher in non-calcareous than in calcareous soils. CONCLUSION: Soil application of fertilizer P and Zn, in soils with low levels of available Zn, should not only aim at increasing the available P and Zn levels but also balancing them at the appropriate Olsen P/ZnDTPA ratio, which was found to lie in the 30-60 range in the present study. © 2020 Society of Chemical Industry.

Measuring the Pancreatic ß Cell Mass in Vivo with Exendin SPECT during Hyperglycemia and Severe Insulitis.

OBJECTIVE: Targeting the glucagon-like peptide-1 receptor with radiolabeled exendin is a very promising method to noninvasively determine the ß cell mass in the pancreas, which is needed to unravel the pathophysiology of type 1 and type 2 diabetes. The present study aimed to explore the effects of both hyperglycemia and insulitis on the uptake of exendin in a spontaneous type 1 diabetes mouse model, nonobese diabetic (NOD) mice. METHODS: NOD mice (n = 75, 7-21 weeks old) were injected intravenously with [111In]In-DTPA-exendin-3, and single-photon emission computed tomography (SPECT) images were acquired 1 h pi. The pancreatic accumulation of [111In]In-DTPA-exendin-3 was quantified in vivo using SPECT and by ex vivo counting and correlated to the ß cell mass (BCM). The influence of insulitis and hyperglycemia on the exendin uptake was assessed. RESULTS: The pancreas could be visualized longitudinally using SPECT. A linear correlation was found between the BCM (%) and pancreatic uptake (%ID/g) as measured by ex vivo counting (Pearson r = 0.64, p < 0.001), which was not affected by either insulitis (Pearson r = 0.66, p = 0.83) or hyperglycemia (Pearson r = 0.57, p = 0.51). Biodistribution and ex vivo autoradiography revealed remaining [111In]In-DTPA-exendin-3 uptake in the pancreas despite total ablation of BCM. CONCLUSIONS: Despite hyperglycemia and severe insulitis, we have found a good correlation between BCM and pancreatic exendin uptake, even in a suboptimal model with relatively high background activity.

Equilibrium, affinity, dissociation constants, IC5O: Facts and fantasies.

The interaction between ligands and receptors is often described in terms of 50% inhibitory concentrations (IC50). However, IC50 values do not accurately reflect the dissociation constants (Kd), and the domain of application and precision of proposed approximations for Kd estimation are unclear. The effect of affinity and of experimental conditions on the differences between IC50 and Kd has been assessed from exact mass action law calculations and from computer simulations. Competitions between [111 In]DTPA-indium and a few metal-DTPA complexes for binding to a specific antibody are discussed as a practical example. Exact calculations of competition assays have been implemented in Microsoft Excel and performed for a variety of concentrations of receptor, tracer, and competitor. The results are identical to those of software packages. IC50 is found larger than Kd by less than 20% only when tracer concentration is small compared with Kd and to the receptor concentration and when this receptor concentration is small compared with Kd. Otherwise, Kd and IC50 may be very different and approximations proposed in the literature to obtain Kd values from graphically derived IC50 are not acceptable as soon as the concentrations of tracer or of receptor approach Kd. Under most experimental conditions, IC50 values do not reflect Kd values. Using available software packages to determine and report Kd values would allow for more meaningful comparisons of results obtained under different experimental conditions.

Biotransformation Capacity of Carboxylesterase in Skin and Keratinocytes for the Penta-Ethyl Ester Prodrug of DTPA.

The penta-ethyl ester prodrug of the chelating agent diethylene triamine pentaacetic acid (DTPA), referred to as C2E5, effectively accelerated clearance of americium after transdermal delivery. Carboxylesterases (CESs) play important roles in facilitating C2E5 hydrolysis. However, whether CESs in human skin hydrolyze C2E5 remains unknown. We evaluated the gene and protein expression of CESs in distinctive human epidermal cell lines: HEKa, HEKn, HaCaT, and A431. The substrates p-nitrophenyl acetate (pNPA) and 4-nitrophenyl valerate (4-NPV) were used to access esterase and CES activity. C2E5 hydrolysis was measured by radiometric high-performance liquid chromatography after incubation of [(14)C]C2E5 with supernatant fractions after centrifugation at 9000g (S9) prepared from skin cell lines. CES-specific inhibitors were used to access metabolism in human skin S9 fractions with analysis by liquid chromatography-tandem mass spectrometry. We identified the human carboxylesterase 1 and 2 (CES1 and CES2) bands in a Western blot. The gene expression of these enzymes was supported by a real-time polymerase chain reaction (qPCR). pNPA and 4-NPV assays demonstrated esterase and CES activity in all the cell lines that were comparable to human skin S9 fractions. The prodrug C2E5 was hydrolyzed by skin S9 fractions, resulting in a primary metabolite, C2E4. In human skin S9 fractions, inhibition of C2E5 hydrolysis was greatest with a pan-CES inhibitor (benzil). CES1 inhibition (troglitazone) was greater than CES2 (loperamide), suggesting a primary metabolic role for CES1. These results indicate that human keratinocyte cell lines are useful for the evaluation of human cutaneous metabolism and absorption of ester-based prodrugs. However, keratinocytes from skin provide a small contribution to the overall metabolism of C2E5.

Development and Characterization of the Recombinant Human VEGF-EGF Dual-Targeting Fusion Protein as a Drug Delivery System.

The design, preparation, as well as structural and functional characterizations of the recombinant fusion protein hVEGF-EGF as a dual-functional agent that may target both EGFR (R: receptor) and angiogenesis are reported. hVEGF-EGF was found to bind to EGFR more strongly than did EGF, and to bind to VEGFR similarly to VEGF. Mass spectrometry measurements showed that the sites of DTPA (diethylenetriaminepentaacetic acid) conjugated hVEGF-EGF (for radiolabeling) were the same as those of its parent hEGF and hVEGF proteins. All DTPA-conjugated proteins retained similar binding capacities to their respective receptors as compared to their respective parent proteins. In vitro cell binding studies using BAEC (a bovine aortic endothelial cell) and MDA-MB-231 (a human breast cancer) cells expressing both EGFR and VEGFR confirmed similar results. Treating BAEC cells with hVEGF-EGF induced remarkable phosphorylation of EGFR, VEGFR, and their downstream targets ERK1/2. Nevertheless, the radiolabeled (111)In-DTPA-hVEGF-EGF showed cytotoxicity against MDA-MB-231 cells. Pharmacokinetic studies using (111)In-DTPA-hVEGF-EGF in BALB/c nude mice showed that appreciable tracer activities were accumulated in liver and spleen. In all, this study demonstrated that the fusion protein hVEGF-EGF maintained the biological specificity toward both EGFR and VEGFR and may be a potential candidate as a dual-targeting moiety in developing anticancer drugs.

A drug-repositioning screening identifies pentetic acid as a potential therapeutic agent for suppressing the elastase-mediated virulence of Pseudomonas aeruginosa.

Pseudomonas aeruginosa, a Gram-negative bacterium of clinical significance, produces elastase as a predominant exoprotease. Here, we screened a library of chemical compounds currently used for human medication and identified diethylene triamine penta-acetic acid (DTPA, pentetic acid) as an agent that suppresses the production of elastase. Elastase activity found in the prototype P. aeruginosa strain PAO1 was significantly decreased when grown with a concentration as low as 20 µM DTPA. Supplementation with Zn(2+) or Mn(2+) ions restored the suppressive effect of DTPA, suggesting that the DTPA-mediated decrease in elastase activity is associated with ion-chelating activity. In DTPA-treated PAO1 cells, transcription of the elastase-encoding lasB gene and levels of the Pseudomonas quinolone signal (PQS), a molecule that mediates P. aeruginosa quorum sensing (QS), were significantly downregulated, reflecting the potential involvement of the PQS QS system in DTPA-mediated elastase suppression. Biofilm formation was also decreased by DTPA treatment. When A549 alveolar type II-like adenocarcinoma cells were infected with PAO1 cells in the presence of DTPA, A549 cell viability was substantially increased. Furthermore, the intranasal delivery of DTPA to PAO1-infected mice alleviated the pathogenic effects of PAO1 cells in the animals. Together, our results revealed a novel function for a known molecule that may help treat P. aeruginosa airway infection.

Chelator-induced phytoextraction of zinc and copper by rice seedlings.

Solution culture was carried to investigate capacity of synthetic aminopolycarboxylic acids (ethylenediamine tetraacetate, N-hydroxyethylenediaminetriacetic acid, and diethylenetriamine-pentaacetate) for enhancing botanical removal and transport of heavy metals (Cu and Zn) by plants. Biodegradable organic acids (citric acid, malic acid, and oxalic acid) were also selected as alternatives to compare them with synthesized chelating agents for effectiveness. Young rice seedlings (Oryza sativa L. cv. XZX 45) were grown in nutrient solutions treated with single or combined metal solutions in presence or absence of chelating compounds. Calculation by chemical equilibrium program VISUAL MINTEQ showed that different chelating compounds had various complex potential with Cu(2+) and Zn(2+) ions, in which synthetic chelators exhibited higher complexed capability than biodegradable organic acids. All applied synthetic aminopolycarboxylic acids significantly decreased removal of metal from nutrient solution (p < 0.01), while more or less effects of organic acids supplied on biosorptive potential were observed with all treatments (p > 0.05), compared with the treatment without metal ligands. Synthetic aminopolycarboxylic acids significantly decreased metal concentrations in plant materials in all treatments (p < 0.01). However, biodegradable organic acids decreased metal concentrations in roots (p < 0.01), but enhanced them in shoots (p < 0.01). Results obtained indicated that synthetic aminopolycarboxylic acids decreased uptake of metals by rice seedlings, but translocation of metals complexed within plant materials was evident. Although exogenous biodegradable organic acids showed negligible effect on botanical removal of metals, metals complexed with organic acids was more mobile than those complexed with other chelating agents. These information collected here had important implication for the use of biodegradable metal chelators in transport of essential micronutrients in plant nutrition.

Modular columnar supramolecular polymers as scaffolds for biomedical applications.

Self-assembly of discotic molecules into supramolecular polymers offers a flexible approach for the generation of multicomponent one-dimensional columnar architectures with tuneable biomedical properties. Decoration with ligands induces specific binding of the self-assembled scaffold to biological targets. The modular design allows the easy co-assembly of different discotics for the generation of probes for targeted imaging and cellular targeting with adjustable ligand density and composition.

Actinide chelation: biodistribution and in vivo complex stability of the targeted metal ions.

Because of the continuing use of nuclear fuel sources and heightened threats of nuclear weapon use, the amount of produced and released radionuclides is increasing daily, as is the risk of larger human exposure to fission product actinides. A rodent model was used to follow the in vivo distribution of representative actinides, administered as free metal ions or complexed with chelating agents including diethylenetriamine pentaacetic acid (DTPA) and the hydroxypyridinonate ligands 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO). Different metabolic pathways for the different metal ions were evidenced, resulting in intricate ligand- and metal-dependent decorporation mechanisms. While the three studied chelators are known for their unrivaled actinide decorporation efficiency, the corresponding metal complexes may undergo in vivo decomposition and release metal ions in various biological pools. This study sets the basis to further explore the metabolism and in vivo coordination properties of internalized actinides for the future development of viable therapeutic chelating agents.

Biochar inhibited hydrogen radical-induced Cd bioavailability in a paddy soil.

Herein, hydrogen (H·) radical was observed as a new pathway to produce hydroxyl (OH·) radicals that promoted cadmium sulfide (CdS) dissolution and thus Cd solubility in paddy soils. In soil incubation experiments, the bioavailable Cd concentrations in flooded paddy soils were increased by 8.44 % as the soil was aerated for 3d. For the first time, the H· radical was observed in aerated soil sludge. The association of CdS dissolution with free radicals was thereafter confirmed in an electrolysis experiment. Both H· and OH· radicals in electrolyzed water were confirmed by the electron paramagnetic resonance analysis. In the system with CdS, water electrolysis increased soluble Cd2+ concentration by 60.92 times, which was compromised by 43.2 % when the radical scavenger was introduced. This confirmed the free radicals can lead to oxidative dissolution of CdS. The H· radical was generated in systems with fulvic acid or catechol irradiated by ultraviolet lights, indicating soil organic carbon could be an important precursor for H· and OH· radicals. Biochar application decreased soil DTPA-Cd by 22-56 % invoking mechanisms besides adsorption. First, biochar quenched radicals and reduced CdS dissolution by 23.6 % in electrolyzed water in which -C-OH of biochar was oxidized to CO. Second, biochar boosted Fe/S-reducing bacteria and thus compromised CdS dissolution, as affirmed by a reversal correlation between soil available Fe2+ and DTPA-Cd concentrations. A similar phenomenon occurred in Shewanella oneidensis MR-1-inoculated soils. This study provided new insights into the bioavailability of Cd and offered feasible measures to remediate Cd-contaminated paddy soils with biochars.

Fibroblast Activation Protein-Targeting Minibody-IRDye700DX for Ablation of the Cancer-Associated Fibroblast with Photodynamic Therapy.

Fibroblast activation protein (FAP), expressed on cancer-associated fibroblasts, is a target for diagnosis and therapy in multiple tumour types. Strategies to systemically deplete FAP-expressing cells show efficacy; however, these induce toxicities, as FAP-expressing cells are found in normal tissues. FAP-targeted photodynamic therapy offers a solution, as it acts only locally and upon activation. Here, a FAP-binding minibody was conjugated to the chelator diethylenetriaminepentaacetic acid (DTPA) and the photosensitizer IRDye700DX (DTPA-700DX-MB). DTPA-700DX-MB showed efficient binding to FAP-overexpressing 3T3 murine fibroblasts (3T3-FAP) and induced the protein's dose-dependent cytotoxicity upon light exposure. Biodistribution of DTPA-700DX-MB in mice carrying either subcutaneous or orthotopic tumours of murine pancreatic ductal adenocarcinoma cells (PDAC299) showed maximal tumour uptake of 111In-labelled DTPA-700DX-MB at 24 h post injection. Co-injection with an excess DTPA-700DX-MB reduced uptake, and autoradiography correlated with FAP expression in the stromal tumour region. Finally, in vivo therapeutic efficacy was determined in two simultaneous subcutaneous PDAC299 tumours; only one was treated with 690 nm light. Upregulation of an apoptosis marker was only observed in the treated tumours. In conclusion, DTPA-700DX-MB binds to FAP-expressing cells and targets PDAC299 tumours in mice with good signal-to-background ratios. Furthermore, the induced apoptosis indicates the feasibility of targeted depletion of FAP-expressing cells with photodynamic therapy.

A phosphoramidate-based prostate-specific membrane antigen-targeted SPECT agent.

BACKGROUND: Prostate-specific membrane antigen (PSMA) remains an active target for imaging and therapeutic applications for prostate cancer. METHODS: In the present study, an irreversible phosphoramidate inhibitor, CTT-54 (IC50 = 14 nM), has been modified to deliver 99mTc-(CO)3-DTPA as a SPECT imaging payload to PSMA+ cells in vivo and in vitro. Percent uptake, competitive binding, and internalization will evaluate the imaging agent in vitro. Preliminary biodistribution and imaging will be utilized for in vivo evaluation. RESULTS: In vitro studies demonstrate that the radiotracer 99mTc-(CO)3-DTPA-CTT-54 exhibits increasing cellular uptake in the PSMA+ LNCaP cells over time. More importantly, it was found that 99mTc-(CO)3-DTPA-CTT-54 is rapidly internalized into LNCaP cells, presumably through the PSMA enzyme-inhibitor complex. In a pilot biodistribution study, increasing accumulation of the radiotracer in LNCaP xenografts was observed from 2 to 4 hr and significant clearance from non-target tissues. CONCLUSIONS: While DTPA may not represent the ideal chelate structure for 99mTc(CO)3, the data provides proof-of-concept support for the development of a next-generation phosphoramidate-based PSMA inhibitor-conjugates for use as SPECT imaging agents.

Differences in predicted and actually absorbed doses in peptide receptor radionuclide therapy.

PURPOSE: An important assumption in dosimetry prior to radionuclide therapy is the equivalence of pretherapeutic and therapeutic biodistribution. In this study the authors investigate if this assumption is justified in sst2-receptor targeting peptide therapy, as unequal amounts of peptide and different peptides for pretherapeutic measurements and therapy are commonly used. METHODS: Physiologically based pharmacokinetic models were developed. Gamma camera and serum measurements of ten patients with metastasizing neuroendocrine tumors were conducted using (111)In-DTPAOC. The most suitable model was selected using the corrected Akaike information criterion. Based on that model and the estimated individual parameters, predicted and measured (90)Y-DOTATATE excretions during therapy were compared. The residence times for the pretherapeutic (measured) and therapeutic scenarios (simulated) were calculated. RESULTS: Predicted and measured therapeutic excretion differed in three patients by 10%, 31%, and 7%. The measured pretherapeutic and therapeutic excretion differed by 53%, 56%, and 52%. The simulated therapeutic residence times of kidney and tumor were 3.1 ± 0.6 and 2.5 ± 1.2 fold higher than the measured pretherapeutic ones. CONCLUSIONS: To avoid the introduction of unnecessary inaccuracy in dosimetry, using the same substance along with the same amount for pretherapeutic measurements and therapy is recommended.

Natural field freeze-thaw process leads to different performances of soil amendments towards Cd immobilization and enrichment.

Cadmium (Cd) soil pollution is a global issue affecting crop production and food safety. Remediation methods involving in-situ Cd immobilization have been developed, but their effectiveness can diminish under seasonal freeze-thaw aging processes. In this study, we assessed the field performance of four soil treatments at a seasonally frozen rice paddy. Amendments were applied at 2 wt%, including: (i) sepiolite (a 2:1 clay mineral), (ii) superphosphate, (iii) biochar (produced by rice husk at 500 °C for 2 h), and (iv) joint application of biochar & superphosphate (1:1 mixture by weight). Immobilization performance was determined as DTPA extractable Cd and plant uptake in various organs. Overall, the four treatments significantly reduced Cd bioavailability during the plant growth period, with average DTPA-extractable concentrations decreasing by 43%, 34%, 39% and 45% for the four treatments, respectively, relative to untreated soil (control). Rice grain yields from the superphosphate and the joint application treatments increased by 8.0% and 11.8%, respectively, and Cd accumulation within those grains reduced by 14.3% and 48.9%, respectively. During the winter non-growth period, freeze-thaw aging facilitated Cd mobilization, with DTPA-extractable Cd increasing by 16.9% in the control soil, relative to the initial period. However, this reduced to 10.9%, 14.4%, 7.6% and 5.0%, for the sepiolite, superphosphate, biochar and joint application treatments, respectively. Overall, the joint application of biochar and superphosphate provided the best performance in terms of both long-term Cd immobilization and rice production enhancement, offering a green remediation option for risk management at Cd contaminated rice paddies in seasonally frozen regions.

Bacterial hydrophilins promote pathogen desiccation tolerance.

Acinetobacter baumannii is a leading cause of hospital-acquired infections, where outbreaks are driven by its ability to persist on surfaces in a desiccated state. Here, we show that A. baumannii causes more virulent pneumonia following desiccation and profile the genetic requirements for desiccation. We find that desiccation tolerance is enhanced upon the disruption of Lon protease, which targets unfolded and aggregated proteins for degradation. Notably, two bacterial hydrophilins, DtpA and DtpB, are transcriptionally upregulated in Δlon via the two-component regulator, BfmR. These proteins, both hydrophilic and intrinsically disordered, promote desiccation tolerance in A. baumannii. Additionally, recombinant DtpA protects purified enzymes from inactivation and improves the desiccation tolerance of a probiotic bacterium when heterologously expressed. These results demonstrate a connection between environmental persistence and pathogenicity in A. baumannii, provide insight into the mechanisms of extreme desiccation tolerance, and reveal potential applications for bacterial hydrophilins in the preservation of protein- and live bacteria-based pharmaceuticals.

Molecular MRI assessment of vascular endothelial growth factor receptor-2 in rat C6 gliomas.

Angiogenesis is essential to tumour progression and a precise evaluation of angiogenesis is important for tumour early diagnosis and treatment. The quantitative and dynamic in vivo assessment of tumour angiogenesis can be achieved by molecular magnetic resonance imaging (mMRI). Vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) are the main regulatory systems in angiogenesis and have been used as hot targets for radionuclide-based molecular imaging. However, little research has been accomplished in targeting VEGF/VEGFRs by mMRI. In our study, we aimed to assess the expression of VEGFR2 in C6 gliomas by using a specific molecular probe with mMRI. The differential uptake of the probe conjugated to anti-VEGFR2 monoclonal antibody, shown by varied increases in T(1) signal intensity during a 2 hr period, demonstrated the heterogeneous expression of VEGFR2 in different tumour regions. Microscopic fluorescence imaging, obtained for the biotin group in the probe with streptavidin-Cy3, along with staining for cellular VEGFR2 levels, laminin and CD45, confirmed the differential distribution of the probe which targeted VEGFR2 on endothelial cells. The angiogenesis process was also assessed using magnetic resonance angiography, which quantified tumour blood volume and provided a macroscopic view and a dynamic change of the correlation between tumour vasculature and VEGFR2 expression. Together these results suggest mMRI can be very useful in assessing and characterizing the expression of specific angiogenic markers in vivo and help evaluate angiogenesis associated with tumour progression.

The interaction of La(3+) complexes of DOTA/DTPA glycoconjugates with the RCA(120) lectin: a saturation transfer difference NMR spectroscopic study.

The study of ligand-receptor interactions using high-resolution NMR techniques, namely the saturation transfer difference (STD), is presented for the recognition process between La(III) complexes of 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane monoamide and diethylenetriaminepentaacetic acid bisamide glycoconjugates and the galactose-specific lectin Ricinus communis agglutinin (RCA(120)). This new class of Gd(III)-based potential targeted MRI contrast agents (CAs), bearing one or two terminal sugar (galactosyl or lactosyl) moieties, has been designed for in vivo binding to the asialoglycoprotein receptor, which is specifically expressed at the surface of liver hepatocytes, with the aim of leading to a new possible diagnosis of liver diseases. The in vitro affinity constants for the affinity of the divalent La(III)-glycoconjugate complexes for RCA(120), used as a simple, water-soluble receptor model, were higher than those of the monovalent analogues. The combination of the experimental data obtained from the STD NMR experiments with molecular modelling protocols (Autodock 4.1) allowed us to predict the mode of binding of monovalent and divalent forms of these CAs to the galactose 1α binding sites of RCA(120). The atomic details of the molecular interactions allowed us to corroborate and supported the interaction of both sugar moieties and the linkers with the surface of the protein and, thus, their contribution to the observed interaction stabilities.

Experimental facts supporting a red marrow uptake due to radiometal transchelation in 90Y-DOTATOC therapy and relationship to the decrease of platelet counts.

PURPOSE: The aim of this study was to retrospectively evaluate whether the red marrow (RM) takes up (111)In-diethylenetriaminepentaacetic acid (DTPA)-D-Phe(1)-octreotide and (86)Y-DOTATOC and to assess the correlation between the RM absorbed doses and platelet count reduction as a biological dose estimate. METHODS: Data from 12 patients who underwent at 24 h p.i. high statistics (111)In single photon emission computed tomography (SPECT) and (86)Y positron emission tomography (PET) acquisitions of the chest were analysed. Uptake was measured on >7 cm spine length and converted to total RM uptake using standard RM distribution in man. RM absorbed doses were calculated assuming specific RM uptake and using the plasma and remainder of the body models. RM doses were correlated with the platelet count reduction at 4 weeks. In vitro experiments explored the metabolism of (111)In-DTPA-D-Phe(1)-octreotide and (90)Y-DOTATOC in plasma. RESULTS: The correlation between the uptake of both tracers was excellent (R = 0.80), indicating that RM uptake of (86)Y-DOTATOC reflects a real physiological process and not reconstruction artefacts. The kinetics of (86)Y-DOTATOC RM activity was different than that in blood and tumours, with no activity at 4 h p.i. indicating that the uptake is not somatostatin receptor dependent. In vitro experiments showed a transchelation of both radiometals to free transferrin that could explain the RM uptake. In patients without chemotherapy and with a normal platelet count recovery, a good correlation (R = 0.96) was found between the RM doses and the platelet count reduction at the nadir. CONCLUSION: These experimental facts support the existence of a true RM uptake likely related to transchelation of the radiometal to transferrin. RM uptake correlates well with the observed acute RM toxicity.

Phytoavailability, human risk assessment and transfer characteristics of cadmium and zinc contamination from urban gardens in Kano, Nigeria.

BACKGROUND: Quantitative data about phytoavailability and transfer into consumed plant parts for heavy metals in intensively managed urban vegetable production areas of sub-Saharan Africa are scarce. We therefore studied the transfer of zinc (Zn) and cadmium (Cd) from soil to the root and subsequent translocation to edible portions of four vegetables in six urban gardens. RESULTS: While respective diethylenetriaminepentaacetic acid (DTPA)-available Zn and Cd concentrations ranged from 18 to 66 mg kg(-1) and from 0.19 to 0.35 mg kg(-1) , respectively, in soils, total Zn and Cd were 8.4-256 mg kg(-1) and 0.04-1.7 mg kg(-1) in shoot parts. Metal transfer factor (MTF) ratios were higher in Zn (0.2-0.9) than in Cd (0.1-0.6). Our data suggest that total Zn concentration in soil is a reliable indicator to assess its transfer from soil to crop in lettuce, carrot and parsley, while for Cd DTPA-extractable concentration may be used to estimate soil-crop transfer of Cd in amaranthus and carrot. Overall, Cd was more easily translocated to the aerial plant parts than Zn. CONCLUSION: Zinc and Cd accumulation by vegetables in our soils is mainly a metabolically controlled process. Such accumulation can contaminate the ecosystem but under our conditions intake and ingestion of these metals will likely have to occur over a prolonged period to experience health hazard.