Treatment and labeling of silica sand for obtaining a prospective solid 99mTc radiotracer

Pretreated silica sand labeling using varying concentrations of tin(II) fluoride and chloride as reducing agents and different times labeling was performed in order to develop a methodology for labeling silica sand with 99mTc for using as solid radiotracer. Influence of different sand pretreatment parameters on the sorption yield (Rret%) was statistically evaluated. The effectiveness of the methods used to reduce pertechnetate (99mTcO4−) by ascending paper chromatography was confirmed. Results show relatively high values of 99mTc sorption yields on silica sand. It was possible to establish a methodology for obtaining solid 99mTc labeled radiotracers in support of silica sand.


Introduction
Radiotracers as a tool for various applications in the industry allow to carry out studies without stopping the technological flow of processes. However, this technique is still underutilized. The main cause is the lack of timely availability of required radiotracer [1]. Studies which expand the potentialities of 99m Tc eluted from 99 Mo/ 99m Tc generator to label silts [2], silica (FS) and zeolite (FZ) supported ferragels, surface waters in non-reducing [3,4], or reducing environment [5], and to trace the organic liquid phase [6], have been carried out in our country. Silica sand and others compounds with a high SiO 2 content are frequently used in industrial applications [7]. On the other hand, processes involving materials of similar density, granulometry and specific weight to the silica sand could also be studied with labeled silica sand [7]. The labeling of silica sand with 99m Tc is shown as an attractive option to ensure the availability of radiotracers required in industrial applications. Experimental 1 g of silica sand and 1 mL of 99m TcO 4 − (ac) eluted from the 99 Mo/ 99m Tc generator with 3 MBq of 99m Tc activity were added in a tube for centrifuge. The mixture was stirred for a period of 15 min. Soon afterwards 2 mL of SnF 2 or SnCl 2 solution (pH = 5) of varying concentration according to experiment, was added. The solution was stirred for a reaction time which varies in each experiment and it was centrifuged for 1 min. Three aqueous phase samples of 0.2 mL were taken and were measured three times with a radiometric system SRN1C-02, coupled to a NaI (Tl) detector. To evaluate 99m Tc retention in the silica sand, the retention degree (R ret% ), was determined indirectly as: where, A l ( cps mL -1 ) and A b ( cps mL -1 ) are the radioactive concentrations of 99m Tc solutions, after and before the contact with the silica sand, respectively. Each experiment was repeated three times for error estimation. Some studies were carried out using experimental designs. In these cases, the error was calculated from three experiments in the center of the experimental plan. Cuban natural silica sand from Silica Sand Industrial Plant of Guane, Pinar del Río, was used. Pretreatment of silica sand was conducted in two main stages. In the first, 15 g of silica sand was put in contact with 15 mL of concentrated nitric acid (HNO 3 ) and the mixture was stirred for 15 min (t HNO3−sand ) in a magnetic stirrer. Vacuum filtration with 25 mL of distilled water was used to separate the silica sand from the liquid phase. After filtered sand spread in a peatry plate and allowed to dry with IR lamp for 30 min. For the second stage the solid was transferred to a beaker in which were added 15 mL of sodium hydroxide (NaOH) 2 mol L − 1 of concentration and kept in touch with constant stirring for 15 min (t NaOH−sand ), filtered under vacuum filtration and the solid was dried with IR lamp for 1 h.
Paper chromatography with acetone as mobile phase was employed to verify the percent of reduced 99m TcO 4 − to 99m Tc colloidal -hydrolyzated ( 99m TcO 2 , 99m TcO(OH) 2 or 99m Tc 2+ ) with SnCl 2 or SnF 2 . Afterwards 2 mL of SnCl 2 or SnF 2 solution of varying concentration were added (according to experiment) to 1 mL of 99m TcO 4 − (ac) and the solution was stirred for the proposed reaction time for each experiment. A drop is removed and placed at the origin of the paper strip, this was placed in the tank to chromatography (glass jars) containing acetone (2 mm deep) with the end of the origin downwards. When the front of the run was moved by the paper strip, this is removed and allowed to dry. The center strip was cut and measured in SRN1C-02 system, coupled to a NaI (Tl) detector [5,6]. To evaluate the reduced 99m Tc retention by chromatography, the reduction yield (R * % ) was determined as: ,where A a (cps mL − 1 ) is the radioactive concentration at the point of application and A f (cps mL − 1 ) is the radioactive concentration in the solvent front. Yields are reported with standard deviations reflect three replicates, and three measurements per replicate for a total of 9 radiometric measurements for each value of R * % . The type of reducing agent (SnCl 2 or SnF 2 ) influence on 99m Tc retention in the silica sand (R ret% ) was evaluated. Two experiments were carried out using 15 min of reaction time and 0.5 mmol L − 1 of concentration for each reducing agent. These conditions were chosen from previous studies results [10,14].
A 2 2 factorial experimental plan was designed to study the influence of SnF 2 concentration and reaction time on 99m Tc retention in the solid. The maximum and minimum values of the plan used were 30 min and 15 min of reaction times, and 2 mmol L − 1 and 0.5 mmol L − 1 of SnF 2 concentrations, respectively. Parameters values were selected taking into account the divergence from bibliographic reports and previous results [10,15].
Some experiments to evaluate the influence on the 99m Tc retention degree of the c(NaOH), relation V(HNO 3 )/m(sand), reaction time between HNO 3 and sand (t HNO3−sand ) and reaction time between NaOH and sand (t NaOH−sand ) used for the pretreatment of the silica sand, were executed. A 2 4 factorial experimental plan was designed. Limits and the middle values of the plan used for each parameter are shown in Table 1. Parameters values were selected taking into account the divergence from bibliographic reports and previous results [10].
The data was processed with STATGRAPHICS Centurion XV software. P values for 5% degree of confidence were selected to determine statistical significance of the principal effects as well as the interactions. Three replicates were performed in the center of the plane to assess the pure error Line 2 -1.0 0.5 10 10 Line 3 0 2.0 1.0 15 15 In order to meet the transformations in silica sand after treatment a study of X-ray spectroscopy coupled to the technique of scanning electron microscopy (SEM-EDS) to samples of silica sand was made before and after treatment. For treatment of it there were employed c(NaOH) = 1 mol L − 1 , V (HNO 3 )/m(sand) = 1.5, t HNO3−sand = 20 min and t NaOH−sand = 20 min

Results and discussion
With the purpose of relating the quantity of reduced 99m TcO 4 − (R * % ) with the obtained retention degree (R ret% ) the chromatographic study of the reduction of the 99m TcO 4 − was carried out. The results show that the reduction yields (R * % ), with both reducing agents, were much higher than retention degrees obtained (Table 2), therefore there is a greater amount of reduced 99m Tc species adsorbed on the surface of silica sand [12,16]. Table 2 shows that obtained values (R ret% ) using SnF 2 are higher by approximately 20% than those obtained under the same conditions using SnCl 2 , probably due to the greater stability of SnF 2 reducing properties [17].
There are different approaches in the literature about the influence of SnF 2 concentration and reaction time on 99m Tc retention in the silica sand [10]. The R ret % obtained from the 2 2 executed experimental design and P values for the principal effects as well as for their interactions are shown in Table 3. From the P value analysis, it was clear that just the variation of reaction time (B) between SnF 2 and 99m TcO 4 − is statistically significant (P = 0.002). There is only a 0.2% probability that variation observed in the R ret% due to variation of parameter B could be by chance. The remaining factors (A and AB) are not statistically significant for a 95% confidence.
The highest 99m Tc sorption yields were obtained for experiments where corresponding reaction times were employed at the minimum level (15 min), indicating that the increase of this factor has a negative effect on the degree of 99m Tc retention. Equation 3 describes the dependency between the R ret% and the studied parameters. Lack of fitting P value (0.6503) greater than 0.05 indicates that the model properly represents the behavior of the R ret% for a 95% of confidence in the studied interval.    . 1 Response surface of the R ret% model calculated with the 2 2 experimental design of reducing agent. This is probably the main cause of the decrease in the degree of retention of 99m Tc in the treated silica sand with increasing to 30 min of reaction time. Table 5 shows the results from 2 4 experimental design. From the P value analysis, it was clear that only factors B (V(HNO 3 )/m(sand)) and C (t HNO3−sand ), within established limits, had significant effects on the degree of 99m Tc retention. So, the observed variations in the R ret% are mainly provoked for the variation of the relation V(HNO 3 )/m(sand) and the reaction time between HNO 3 and sand.
Indeed, higher R ret% values were obtained in experiments 1, 10, 17 and 19, which matched the maximum of V(HNO 3 )/m(sand) and t HNO3−sand , and the experiment 2, which corresponds to maximum value of t HNO3−sand , all obtained values are above 70%. Figure 2 shows the semi-quantitative analysis of the composition of the silica sand sample before and after treatment, obtained by X-ray spectroscopy coupled to the technique Microscopy Scanning Electron Microscopy (SEM-EDS).
These results show the effect of each stage of the treatment, the first with HNO 3 to clean the sand of organic matter, which is reflected in the study with the variation of the contents of oxygen and carbon. With the removal of these impurities are released pores on the surface of the grains that were previously occupied by them. During the second stage (treatment with NaOH) can modify the crystalline structure Response surface of the R ret% model calculated is shown in Fig. 1. This allows to predict the R ret% with the variation of the factors within limits established in the design.
The results of chromatographic study in order to explore the cause of the negative effect of reaction time on the degree of 99m Tc retention (Table 4) show a decrease in the values of R * % with increasing reaction time for both concentrations 30 2 82 ± 2 It is possible that with increasing reaction time the reduced 99m Tc is re-oxidized and become part of the solution, then the retention degree of 99m Tc decrease. The labeling of the silica sand was performed after each stage of treatment in order to determine the influence of these stages on the 99m Tc sorption yields. Withholding grades earned during each stage of treatment were 35 ± 1% for reaction with HNO 3 (conc) , 37 ± 2% for the attack with NaOH (concentration of 2 mol L − 1 ) and 70 ± 2% for the full treatment, showing that the two stages of treatment have great significance sand, each being responsible for approximately 50% of the value of R ret% obtained. Therefore, it is convenient to study the influence of several parameters related with both stages of the treatment of the sand silica in the degree of retention of the 99m Tc 73.9 ± 0.5 The effect of t NaOH−sand parameter is not excluded from the analysis because their P-value shows that only 23% of the R ret% variation due to the variation of this factor from the minimum level to the maximum is due to chance. It is recommended to keep at its highest level. With the increase over the initial methodology pretreatment sand of relation V(HNO 3 )/m(sand) from 1 to 1.5 and t HNO3−sand in 5 min (from 15 to 20 min) is achieved increase R ret% to about 5% (from 69.2 ± 0.2% to 74.5 ± 0.5%) as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons. org/licenses/by/4.0/. of SiO 2 , thereby increasing the available sites for adsorption. This is reflected from the silicon content decreased as from forming a gel of soluble silicate, this contact is washed with water and no longer part of the crystal structure [18]. The results discussed above suggest that the R ret% increased after treatment, are mainly due to the observed changes in silica sand chemical composition and structure.

Conclusions
The retention degree of 99m Tc increase from 48.7 ± 1.4% when SnCl 2 is used as reducing agent to 69.1 ± 0.1% with SnF 2 . So, the obtained results indicate that SnF 2 is prospective for the labeling procedure. It can be stated with 95% confidence that in the range studied, the reaction time between SnF 2 and 99m TcO 4 influences negatively on the labeling of treated silica sand, while the concentration of SnF 2 does not influence. It is recommended to use 15 min as reaction time and c(SnF 2 ) = 0.5 mmol L -1 for labeling. The SEM-EDS analysis showed that the pretreatment of silica sand favors the 99m Tc retention, probably due to the changes observed in its chemical composition and structure. Using 20 min for both reaction times (t HNO3-sand and t NaOHsand ), relation V(HNO 3 )/m(sand) = 1.5 and c(NaOH) = 1 mol L -1 for silica sand treatment a 99m Tc retention degree of 74.5 ± 0.5% could be obtained. From the obtained results for treatment and labeling of Cuban silica sand, it was possible to establish an optimum methodology to obtain a solid 99m Tc radiotracer for industry purposes. work under the Coordinated Research Project (CRP) Radiometric Methods for Measuring and Modeling Multiphase Systems towards Industrial Processes.

Funding Open access funding provided by University of Geneva
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format,