Influence of Alumina Phases on the Molybdenum Adsorption Capacity and Chemical Stability for 99 Mo / 99 mTc Generators Columns

Technetium-99m is the clinically most used radionuclide worldwide. Although many techniques can be applied to separate 99Mo and 99mTc, the most commonly used method is the column chromatography with alumina as stationary phase. However, the alumina nowadays used has limited adsorption capacity of molybdate ions which implies the need to develop or improve materials to produce high specific activity generators. In this paper, alumina was obtained by a solid state method and heat treatments at different conditions. The powders had a microstructure with porous particles of γ, δ, θ and α-Al2O3 phases as well as specific surface area between 36 and 312 m2 g-1. Most interesting results were reached by powders calcined at 900oC for 5 hours which had high chemical stability and a molybdenum adsorption capacity of 92.45 mg Mo per g alumina.


Introduction
99m Tc has been successfully used in several nuclear medicine applications, such as cardiology and oncology.The important position of 99m Tc is owing to its nuclear properties that make possible the ready availability of 99m Tc radiopharmaceuticals from generators based on the low decay of 99 Mo to 99m Tc with short half-life (6 hours) 1 .As well as this, gamma rays with adequate power (140 keV) for singlephoton emission computed tomography (SPECT) can be readily collimated, allowing better location and minimizing the whole body dose 2,3 .
The parent radioisotope ( 99 Mo) can be produced by irradiation of 235 U with thermal or fast neutrons or by irradiation of metallic molybdenum or molybdenum oxide (MoO 3 ) with neutrons.In the first case, the 99 Mo is produced together with other fission products, requiring separation by different techniques.In the second case, little processing is required but only a small portion of 98 Mo is converted to 99 Mo [4][5][6] .Hence, the use of 99 Mo produced by irradiadion of molybdenum, in generator columns, limits the activity of 99m Tc eluates since 99 Mo/ 99m Tc generators are formed by chromatography in which 99 MoO 4 2-is adsorbed on an alumina column 7 .In other words, to obtain generators with adequate specific activity, it is necessary to use molybdenum of high activity obtained by the 235 U fission.
Therefore, in order to use molybdenum produced by neutron activation in 99 Mo/ 99m Tc generators, the adsorbent material used in the column should be modified because alumina has an adsorption capacity limited to 20 mg Mo per g alumina.Many studies have been attempted to develop a material with better performance than alumina but many problems related to the synthesis and to some characteristics of the material have been found [8][9][10][11][12] .This study evaluates the influence of the different alumina phases on the molybdenum adsorption capacity and chemical stability in physiological saline in order to use in 99 Mo/ 99m Tc generators.
The calcined powder was treated in a 0.5 M hydrochloric acid solution for 24 hours under constant agitation at 480 rpm, washed with distilled water, filtered and dried at 100°C for 24 hours.

Physical measurements
In order to determine the thermal events during the increase of temperature, thermal analysis (thermogravimetry, TG and differential scanning calorimetry, DSC) measurements were performed under air flow at a heating rate of 10 o C/ min up to 1000 o C.
Each synthesized powder was analyzed by X-ray powder diffraction (Siemens D5000 diffractometer X-ray, radiation CuKα) to identify the crystalline alumina phases.Also, the specific surface area of the materials was determined using Micromeritics equipment and the equation of Brunauer-Emmett-Teller (BET).The morphology and porosity of the powders were observed by scanning electron microscopy (Philips XL30 and Jeol JSM6701F microscopes).

Evaluation of Molybdenum Absorption Capacity
The molybdenum adsorption capacity was measured by stirring a suspension containing 0.1 g of the calcined powder and 30 ml of ammonium molybdate solution (1 mg/ml) with a pH of 1.5.After 30 minutes under stirring, the suspension was filtered and analyzed by ICP-OES to determine the Mo concentration.

Chemical Stability Tests
For chemical stability tests, chromatographic columns containing 4g of material were conditioned with 250 ml of HCl with pH of 1.5.6 ml of physiological saline solution was passed through the column and collected to determine the aluminum content by colorimetric assay using Chromoazurol S like indicator.

Results and Discussion
Thermal analyses of the dried uncalcined precursor are shown in Figure 1.The results show five endothermic peaks between 70 and 200 o C related to 11.6 wt.% of water loss and the peak found at 297 o C is due to the decomposition of ammonium nitrate with a 61 % of mass loss.An exothermic event found at 310 o C is related to the rapid release of gases due to the oxidation of ammonium nitrate 14 .The evolution of the alumina phases for different heat treatments can be verified from powder diffraction patterns (Figure 2).Based on Figure 2, it is clear the dependence on polymorphic transformations in alumina with the temperature.From data shown in Table 1, it is noted that the heat treatments carried out at lower temperatures resulted in powders with a larger specific surface area, suggesting that the transition alumina phases have higher reactivity.The material calcined at 1000 o C for 5 hours, for example, had a value of specific surface area four times smaller than that calcined at 900 o C for 5 hours due to the presence of α-Al 2 O 3 phase (Figure 2).SEM images of the powders in Figure 3 show that the synthesis method results in highly porous powders, which corroborates with the high surface area determined by BET.Further analysis correlating the microstructure and the crystalline phase determined by XRD makes clear the effect of alumina phases on the surface's morphology and consequently on the surface area.From Figure 4, it is observed that the powder calcined at 900°C/5h (Figure 4a) shows a texturized morphology, typical of transition alumina phases.Powders calcined at 1000 o C/5h (Figure 4b), although exhibit areas with similar texturized morphology, also contain some coalesced regions that can be attributed to α-Al 2 O 3 particles.The heat treatment performed at 1000 o C for 5 hours led to material densification, noted by the lower porosity (Figure 4b), in agreement with the decrease in the surface area measured.In addition, the molybdenum absorption capacity of the powders (Table 2) was directly affected by their surface characteristics.The highest values achieved by materials calcined at 700 o C for 2 hours are associated with the presence of gamma phase, high porosity and high specific surface area.While the lowest adsorption capacity was found for the calcined material at 1000 o C for 5 hours due to the lower specific surface area and lower porosity resultant from the predominance of the α-Al 2 O 3 phase.Considering the studied powders, those treated at 900 o C for 5 hours shown an intermediate adsorption capacity but the value was noteworthy (92.45 mg/g) compared with the limit of 20 mg/g reported for alumina currently used in 99 Mo/ 99m Tc generators.Table 3 presents the results of chemical stability tests that are of great importance for the proposed application because the elutions carried out to separate 99m Tc from 99 Mo use saline physiological solution as eluant.Data in Table 3 show that powders calcined at 700 o C for 2 hours produced a solution with high aluminum content what evidences to be unsuitable for use in 99 Mo/ 99m Tc generator.Besides, this result indicates that the γ-Al 2 O 3 phase has a higher solubility in physiological saline than the other phases of alumina.Chakravarty et al. 13 obtained conflicting results since they found lower than 1 ppm of aluminum when chemical stability tests were performed with acids and bases in powders calcined at 700 o C for 2 hours.The presence of θ-Al 2 O 3 in the calcined material at 900°C for 5 hours was enough to reduce the solubility for levels lower than 2 ppm of aluminum, identical to those found for the calcined material at 1000 o C for 5 hours mainly constituted by α-Al 2 O 3 .However, the low molybdenum absorption capacity of the powder treated at 1000 o C for 5 hours turns impracticable its application for high activity 99 Mo/ 99m Tc generator columns.

Conclusions
The synthesis of alumina from the grind of aluminum nitrate and ammonium carbonate followed by drying and calcination can produce highly porous powders.The results showed that the temperature of calcination affected the alumina formed phases, microstructure, chemical stability and molybdenum adsorption capacity.
The heat treatment performed at 700°C for 2 hours promoted the formation of powder with γ-Al 2 O 3 phase and textured morphology.These characteristics led to high specific surface, high molybdenum adsorption capacity but low chemical stability, making the material inappropriate for use in 99 Mo/ 99m Tc generators columns.
On the other hand, materials calcined at 1000 o C for 5 hours had a great chemical stability but low values of surface specific area and molybdenum adsorption capacity because of the presence of the α-Al 2 O 3 phase and the lower porosity.
The best results were found for the powder calcined at 900 o C for 5 hours.The presence of θ-Al 2 O 3 and γ-Al 2 O 3 led to a relatively high surface area, high chemical stability and high molybdenum adsorption capacity making it promising to be applied as adsorbents in high activity 99 Mo/ 99m Tc generators columns.

Acknowledgements
The authors are highly grateful to Dr. Neuza Taeko Okasaki Fukumori and Dr. Margareth Mie Nakamura Matsuda for their help with ICP analysis.

Figure 1 :
Figure 1: Thermal analysis of the material dried at 100 ° C for 24 hours: (a) TG and (b) DSC.

Figure 2 :
Figure 2: Powder diffraction patterns of the samples heat treated at 700 °C/2h, 900°C/5h and 1000 °C/5h.The heat treatment performed at 700 °C for 2 hours was enough to transform the precursor to γ-Al 2 O 3 .Increasing the temperature and time to 900 o C for 5 hours, we observed the presence of θ and γ-Al 2 O 3 phases, while the treatments performed at 1000 o C for 5 hours presented δ-Al 2 O 3 and α-Al 2 O 3 as transition and stable phases, respectively.The transition phases of alumina are considered advantageous to application as adsorbents in chromatography columns of 99 Mo/ 99m Tc generators due to the higher surface reactivity.From data shown in Table1, it is noted that the heat treatments carried out at lower temperatures resulted in powders with a larger specific surface area, suggesting that the transition alumina phases have higher reactivity.The material calcined at 1000 o C for 5 hours, for example, had a value of specific surface area four times smaller than that calcined at 900 o C for 5 hours due to the presence of α-Al 2 O 3 phase (Figure2).

Table 1 :
Specific surface area (S) of the synthesized powders.

Table 3 :
Content of aluminum present in the saline solution after chemical stability test.