In the presence of fluoride, free Sc³âº is not a good predictor of Sc bioaccumulation by two unicellular algae: possible role of fluoro-complexes.

We investigated the effect of fluoride complexation on scandium accumulation by two unicellular algae, Chlamydomonas reinhardtii and Pseudokirchneriella subcapitata. This trivalent metal was selected for its chemical similarities with aluminum and for its convenient radioisotope (Sc-46), which can be used as a tracer in short-term bioaccumulation studies. Scandium surface-bound concentrations (Sc(ads)) and uptake fluxes (J(int)) were estimated in the two algae over short-term (<1 h) exposures at pH 5 and in the presence of 0 to 40 µM F(-). Although the computed proportion of dissolved Sc(3+) dropped from 20% to 0.01% over this [F(-)] range, Sc(ads) and J(int) values for both algae decreased only slightly, suggesting a participation of Sc fluoro-complexes in both processes. Surface adsorption and uptake of fluoride complexes with aluminum have been reported in the literature. These observations are not taken into account by current models for trace metal bioaccumulation (e.g., the biotic ligand model). Results from a previous study, where the effects of pH on Sc uptake were investigated, suggested that Sc hydroxo-complexes were internalized by C. reinhardtii. There is thus growing evidence that the free ion concentration may not be adequate to predict the accumulation of Sc (and potentially of other trivalent metals) in aquatic organisms.

The biotic ligand model can successfully predict the uptake of a trivalent ion by a unicellular alga below pH 6.50 but not above: possible role of hydroxo-species.

In many reported cases, the biotic ligand model (BLM) has been shown to predict the bioavailability of divalent metals toward aquatic biota successfully. However, studies on the bioavailability of nonessential trivalent metals, including aluminum (Al), are relatively scarce. In the present study, short-term scandium (Sc) internalization fluxes (Jint) were measured in Chlamydomonas reinhardtii in order to explore the applicability of the BLM to trivalent metals. Scandium was selected for its chemical similarities with Al and for its convenient radio-isotope (Sc-46). Apparent affinity constants of Sc(3+) with membrane transport sites (KSc-Rcell app) were surprisingly high, ranging from 10(8.08) M(-1) to 10(13.95) M(-1) over the pH range from 4.50 to 7.90. The competition of H(+) for binding with Sc(3+) transport sites explained this trend within the pH range of 4.50 to 6.00, but not from pH 6.50-7.90. In this latter pH range, predicted fluxes were smaller than observed fluxes and this divergence increased with pH, from a factor of 4 to approximately 1000. Above pH 6.50, the calculated supply of Sc(3+) to the biointerface by physical diffusion of the free Sc(3+) ion and by the dissociation of its hydroxo-complexes (ScOH(2+), Sc(OH)2(+) and Sc(OH)3) was insufficient to support the high observed internalization fluxes. We speculate that this failure of the BLM could be due to the transmembrane transport of undissociated Sc hydroxo-complexes. Scandium uptake could be modeled reasonably well using a simple semiempirical equation considering equal contributions from Sc(3+), ScOH(2+), Sc(OH)2(+), and Sc(OH)3 and no H(+) competition. Our work highlights the importance of studying the possible role of hydroxo-species in trace metal uptake.

Uptake and subcellular partitioning of trivalent metals in a green alga: comparison between Al and Sc.

Despite 40+ years of research on aluminum (Al) toxicity in aquatic organisms, Al transport mechanisms through biological membranes, and the intracellular fate of Al once assimilated, remain poorly understood. The trivalent metal scandium shares chemical similarities with Al and, unlike Al, it has a convenient radioactive tracer (Sc-46) allowing for relatively simple measurements at environmentally relevant concentrations. Thus, we investigated the potential of Sc to substitute for Al in uptake and intracellular fate studies with the green alga Chlamydomonas reinhardtii. Short-term (<60 min) competitive uptake experiments indicated that Al does not inhibit Sc influx, implying that these metals do not share a common transport mechanism. Also, internalized Al concentrations were ~4 times higher than Sc concentrations after long-term (72 h) exposures under similar conditions (4.5 µM AlT or ScT, 380 µM FT, pH 7.0, 3.8 pM Al calc (3+) and 1.0 pM Sc calc (3+) ). However, interesting similarities were observed in their relative subcellular distributions, suggesting possible common toxicity/tolerance mechanisms. Both metals mostly distributed to the organelles fraction and almost no association was found with the cytosolic proteins. The greatest difference was observed in the cellular debris fraction (membranes and nucleus) where Al was much more concentrated than Sc. However, it is not clear whether or not this fraction contained extracellular metal associated with the algal surface. To summarize, Sc does not seem to be an adequate substitute of Al for transport/uptake studies, but could be for investigations of toxicity/tolerance mechanisms in C. reinhardtii. Further work is needed to verify this latter suggestion.

The preparation, biodistribution, and human's absorbed dose evaluation of Radio-Scandium-HYNIC-TOC for somatostatin-receptor-positive neuroendocrine tumors therapy by animal study.

BACKGROUND: Most of the neuroendocrine tumors (NETs) express Somatostatin receptors (SSTr), which are the main bases for the development of several radiopharmaceuticals for therapy and imaging of these types of tumors. In this study, 46 Scandium nuclide was used to label a peptide compound via hydrazinonicotinyl-Tyr3-Octreotide (HYNIC-TOC) and researched further for somatostatin-receptor NETs treatment. METHODS AND MATERIALS: The labeling procedure was conducted at 95°C for 10 min. The compound stability was tested in the environment of human serum at 37°C. The biodistribution of compound was investigated in balb/c normal mice and mice bearing AR4-2J tumor. Absorbed Doses of Human Organs were estimated by extrapolation of the biokinetics data of compound in mice to human's organs and then the absorbed doses were estimated by application of MATLAB and MIRDOSE software. RESULTS: Labeling yield was more than 90% with 555 MBq/mg specific activity. The radio-labeled compound expressed well consistency in human serum. The tumor uptake reached 3.831 ID/g% until 4 h post-injection and increased to 5.564%ID/g until 24 h post-injection. CONCLUSION: The main achievement of this study was high tumor uptake of 46 Sc-HYNIC-TOC which may be therapeutically valuable for the therapy of NETs. The estimation of the absorbed dose of human from 47 Scandium-HYNIC-TOC showed low absorbed doses in critical organs and the elimination of the radiopharmaceutical was through the gastrointestinal tract.

Scandium stimulates the production of amylase and bacilysin in Bacillus subtilis.

We investigated the effects of rare earth elements on enzyme production and secondary metabolism in Bacillus subtilis. Addition of scandium to the growth medium stimulated the production of both amylase and bacilysin at the transcriptional level, thus showing scandium to have a remarkable impact in B. subtilis.

Stability, targeting, and biodistribution of scandium-46- and gallium-67-labeled monoclonal antibody in erythroleukemic mice.

Using a monoclonal antibody specific for the Mr 70,000 glycoprotein of Rauscher erythroleukemia virus, we have determined the optimal conditions for conjugation with the cyclic anhydride of diethylene triamine pentaacetic acid and subsequent labeling with 46Sc. The conjugates were shown to retain their specificity and activity in vitro and to target specifically to virus-infected spleen cells in vivo. The stability of the 46Sc:diethylene triamine pentaacetic acid-antibody conjugates in vivo was studied using immunoaffinity chromatography; 25% of the isotope bound to transferrin, and 75% remained bound to the antibody conjugates. These results are discussed with respect to the potential for labeling antibodies with 47Sc for use in imaging and therapy. Studies with 111In-labeled antibody were used for comparison. Labeling with 67Ga was also performed; these labeled conjugates showed adventitious binding of isotope to the antibody and lack of stability of diethylene triamine pentaacetic acid-chelated gallium. Free EDTA was shown to stably incorporate 67Ga.

Competitive inhibition and selectivity enhancement by Ca in the uptake of inorganic elements (Be, Na, Mg, K, Ca, Sc, Mn, Co, Zn, Se, Rb, Sr, Y, Zr, Ce, Pm, Gd, Hf) by carrot (Daucus carota cv. U.S. harumakigosun).

We investigated the uptake of inorganic elements (Be, Na, Mg, K, Ca, Sc, Mn, Co, Zn, Se, Rb, Sr, Y, Zr, Ce, Pm, Gd, and Hf) and the effect of Ca on their uptake in carrots (Daucus carota cv. U.S. harumakigosun) by the radioactive multitracer technique. The experimental results suggested that Na, Mg, K, and Rb competed for the functional groups outside the cells in roots with Ca but not for the transporter-binding sites on the plasma membrane of the root cortex cells. In contrast, Y, Ce, Pm, and Gd competed with Ca for the transporters on the plasma membrane. The selectivity, which was defined as the value obtained by dividing the concentration ratio of an elemental pair, K/Na, Rb/Na, Be/Sr, and Mg/Sr, in the presence of 0.2 and 2 ppm Ca by that of the corresponding elemental pair in the absence of Ca in the solution was estimated. The selectivity of K and Rb in roots was increased in the presence of Ca. The selectivity of Be in roots was not affected, whereas the selectivity of Mg was increased by Ca. These observations suggest that the presence of Ca in the uptake solution enhances the selectivity in the uptake of metabolically important elements against unwanted elements.

[Leaching of Rare Earth Elements from Coal Ashes Using Acidophilic Chemolithotrophic Microbial Communities].

A method for leaching rare earth elements from coal ash in the presence of elemental sulfur using communities of acidophilic chemolithotrophic microorganisms was proposed. The optimal parameters determined for rare element leaching in reactors were as follows: temperature, 45 degrees C; initial pH, 2.0; pulp density, 10%; and the coal ash to elemental sulfur ratio, 10 : 1. After ten days of leaching, 52.0, 52.6, and 59.5% of scandium, yttrium, and lanthanum, respectively, were recovered.

Studies of the in vivo entry of Ga-67 into normal and malignant tissue.

Previous studies of the effect of scandium on the tissue distribution of Ga-67 suggest that Ga-67 makes its initial in vivo entry into normal and malignant tissues by different routes. (Scandium blocking of plasma protein Ga-67 binding increased Ga-67 excretion, decreased its uptake in normal tissues, but had little effect on rodent tumors.) In further studies we have used other methods to alter the plasma binding of Ga-67. Iron saturation of plasma produced effects on Ga-67 tissue distribution similar to those observed with scandium. On the other hand, increasing Ga-67 plasma binding through induction of anemia and administration of apotransferrin produced the reverse of the effects observed with scandium and iron. We conclude that the initial in vivo entry of Ga-67 into tumor tissue involves mainly an unbound or loosely bound form of Ga-67, whereas its uptake by normal soft tissues is strongly promoted by its binding to transferrin.

Metabolism and possible health effects of aluminum.

Literature regarding the biochemistry of aluminum and eight similar ions is reviewed. Close and hitherto unknown similarities were found. A hypothetical model is presented for the metabolism, based on documented direct observations of Al3+ and analogies from other ions. Main characteristics are low intestinal absorption, rapid urinary excretion, and slow tissue uptake, mostly in skeleton and reticuloendothelial cells. Intracellular Al3+ is probably first confined in the lysosomes but then slowly accumulates in the cell nucleus and chromatin. Large, long-lived cells, e.g., neurons, may be the most liable to this accumulation. In heterochromatin, Al3+ levels can be found comparable to those used in leather tannage. It is proposed that an accumulation may take place at a subcellular level without any significant increase in the corresponding tissue concentration. The possible effects of this accumulation are discussed. As Al3+ is neurotoxic, the brain metabolism is most interesting. The normal and the lethally toxic brain levels of Al3+ are well documented and differ only by a factor of 3-10. The normal brain uptake of Al3+ is estimated from data on intestinal uptake of Al3+ and brain uptake of radionuclides of similar ions administered intravenously. The uptake is very slow, 1 mg in 36 years, and is consistent with an assumption that Al3+ taken up by the brain cannot be eliminated and is therefore accumulated. The possibility that Al3+ may cause or contribute to some specific diseases, most of them related to aging, is discussed with the proposed metabolic picture in mind.

Adhesion of water-borne particulates on freshwater biota.

The retention of suspended particles transported by river flow on surfaces of freshwater plants is a potentially important process in the contamination of aquatic biota. Field experiments have been performed to test the role of benthic algae (periphyton) in trapping inorganic suspended solids transported by the river water and to discriminate between the caesium content of periphyton caused by the adherence of inorganic solids and by the active uptake inside the organisms. The contribution of caesium of suspended solids adhering to biotic surfaces was estimated by determining the scandium content (scandium method). The scandium method was used because this element is geologically ubiquitous in soils and it is not taken up actively by plants and other organisms. The mass of suspended particles retained on the surfaces of microorganisms growing on submerged substrates were determined by comparing the scandium content of suspended material with that in algal communities. Neutron activation analysis was used as the analytical method for determination for both scandium, and caesium. The results indicate that the suspended particle fraction can contribute up to 80% of the caesium contamination of periphyton samples. Active caesium uptake and accumulation by aquatic biota represents the remaining 20% of the total caesium contamination.

The accumulation of the rare earth elements and of scandium in successive needle age classes of Norway spruce.

The endogenous concentrations of Sc, La, Ce, Sm, Eu, Tb, Yb, and Lu were determined by neutron activation analysis in up to five successive needle age classes of Norway spruce (Picea abies). Trees from nine sites over different bedrocks were sampled individually. Concentration values found are generally much lower than those reported in the literature. This is attributed to the careful removal of any aerosols or soil particles from the needle surface prior to analysis. The concentration of each element increases linearly with the needle age class, i.e., the accumulation can be characterized by just one parameter, the yearly increment. This pattern is followed at small as well as at large concentrations. The accumulation behavior of the investigated elements is identical to that of Si. The relative concentrations of the rare earth elements (REE) in the needles are similar to those in the earth crust. There are significant correlations between the individual REE and between Sc and La.

Biological evaluation of trace element data in human ovaries by statistical analysis.

Analysis of variance, analysis of covariance, correlation coefficient, multiple correlation, and partial correlation coefficient statistical tests were applied to Cs, Cr, Co, Fe, Rb, Sc, Se, and Zn content in human ovaries in order to evaluate statistically the possible relationships between these trace elements at: the ovary as an organ, each ovarian phase separately, each morphological part independent of the ovarian phase, and between cortex and medulla within the ovarian phases. The element Cs seems to have a homogeneous distribution between cortex and medulla within reproductive and menopausal phase. Zinc shows a trend to have an antagonistic relation with Cs, Cr, Co, and Fe during fetal and reproductive phases and not during menopausal phase. The relationship between Zn and Cs when Fe is kept constant could be used as a tool for the decontamination of the ovary from an abnormal Cs content or for the inhibition of the accumulation of the same element to the ovarian tissue.

Promises of cyclotron-produced 44Sc as a diagnostic match for trivalent ß--emitters: in vitro and in vivo study of a 44Sc-DOTA-folate conjugate.

UNLABELLED: In recent years, implementation of (68)Ga-radiometalated peptides for PET imaging of cancer has attracted the attention of clinicians. Herein, we propose the use of (44)Sc (half-life = 3.97 h, average ß(+) energy [Eß(+)av] = 632 keV) as a valuable alternative to (68)Ga (half-life = 68 min, Eß(+)av = 830 keV) for imaging and dosimetry before (177)Lu-based radionuclide therapy. The aim of the study was the preclinical evaluation of a folate conjugate labeled with cyclotron-produced (44)Sc and its in vitro and in vivo comparison with the (177)Lu-labeled pendant. METHODS: (44)Sc was produced via the (44)Ca(p,n)(44)Sc nuclear reaction at a cyclotron (17.6 ± 1.8 MeV, 50 µA, 30 min) using an enriched (44)Ca target (10 mg (44)CaCO3, 97.00%). Separation from the target material was performed by a semiautomated process using extraction chromatography and cation exchange chromatography. Radiolabeling of a DOTA-folate conjugate (cm09) was performed at 95°C within 10 min. The stability of (44)Sc-cm09 was tested in human plasma. (44)Sc-cm09 was investigated in vitro using folate receptor-positive KB tumor cells and in vivo by PET/CT imaging of tumor-bearing mice RESULTS: Under the given irradiation conditions, (44)Sc was obtained in a maximum yield of 350 MBq at high radionuclide purity (>99%). Semiautomated isolation of (44)Sc from (44)Ca targets allowed formulation of up to 300 MBq of (44)Sc in a volume of 200-400 µL of ammonium acetate/HCl solution (1 M, pH 3.5-4.0) within 10 min. Radiolabeling of cm09 was achieved with a radiochemical yield of greater than 96% at a specific activity of 5.2 MBq/nmol. In vitro, (44)Sc-cm09 was stable in human plasma over the whole time of investigation and showed folate receptor-specific binding to KB tumor cells. PET/CT images of mice injected with (44)Sc-cm09 allowed excellent visualization of tumor xenografts. Comparison of cm09 labeled with (44)Sc and (177)Lu revealed almost identical pharmacokinetics. CONCLUSION: This study presents a high-yield production and efficient separation method of (44)Sc at a quality suitable for radiolabeling of DOTA-functionalized biomolecules. An in vivo proof-of-concept study using a DOTA-folate conjugate demonstrated the excellent features of (44)Sc for PET imaging. Thus, (44)Sc is a valid alternative to (68)Ga for imaging and dosimetry before (177)Lu-radionuclide tumor therapy.

The effect of age on Ag, Co, Cr, Fe, Hg, Rb, Sb, Sc, Se, and Zn contents in intact human prostate investigated by neutron activation analysis.

The effect of age on trace element contents in intact prostate of 64 apparently healthy 13-60 years old men was investigated by neutron activation analysis. Mean values (M±SΕΜ) for content (mg/kg, dry weight basis) of trace elements were: Ag-0.057±0.007, Co-0.036±0.003, Cr-0.48±0.06, Fe-96.9±6.2, Hg-0.045±0.006, Rb-12.5±0.6, Sb-0.050±0.005, Sc-0.020±0.003, Se-0.63±0.03, and Zn-548±55, respectively. A tendency of age-related increase in Co, Fe, Hg, Sc, and Zn content was observed.