Applied Radiation and Isotopes 70 (2012) 51–58

Contents lists available at ScienceDirect

Applied Radiation and Isotopes

0969-80

doi:10.1

n Corr

E-m

journal homepage: www.elsevier.com/locate/apradiso

Development of a 99Mo/99mTc generator using alumina microspheres forindustrial radiotracer applications

Ashutosh Dash a,n, Rubel Chakravarty a, Ramu Ram a, K.T. Pillai b, Yugandhara Y. Yadav a, D.N. Wagh c,Rakesh Verma c, Sujoy Biswas d, Meera Venkatesh a

a Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, Indiab Fuel Chemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, Indiac Analytical Chemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, Indiad Uranium Extraction Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India

a r t i c l e i n f o

Article history:

Received 26 October 2009

Received in revised form

18 July 2011

Accepted 21 July 2011Available online 29 July 2011

Keywords:

Alumina microspheres

Energy dispersive X-ray fluorescence

(EDXRF)99Mo/99mTc generator

Radiotracer

Sol–gel process

43/$ - see front matter & 2011 Elsevier Ltd. A

016/j.apradiso.2011.07.012

espondening author. Fax: þ91 22 25505151.

ail address: adash@barc.gov.in (A. Dash).

a b s t r a c t

A chromatographic 99Mo/99mTc generator for industrial applications has been developed using alumina

microspheres synthesized through sol–gel process to obtain 99mTc in both aqueous and non-aqueous

media. The sorbent was mesoporous, mechanically strong and possessed high surface area. 99mTc could

be eluted from generator system using either acetone or 0.9% NaCl solution with appreciably high

yields and high radiochemical as well as radionuclidic purity. The facile, versatile generator provides an

efficient way to access 99mTc at industrial sites for radiotracer applications.

& 2011 Elsevier Ltd. All rights reserved.

1. Introduction

Radiotracers are extensively used in the industries to optimizeprocesses, trouble-shooting and improve product quality. Thetechnical and economic benefits of the radiotracer technologyhave been well demonstrated and recognized by the industrialsectors throughout the world (Ram et al., 2009; Pant et al., 2001;Charlton, 1986; Gilath, 1977). The use of short-lived radioisotopesfor industrial applications has several constraints, including theneed for very quick transportation and frequent shipments. Theexpansion of radiotracer technologies in industries could besubstantially catalyzed by the availability of short-lived tracers.In this context, ‘‘radionuclide generators’’, wherever feasible,could be an attractive option for availing the desired radiotracerat the industrial site.

99mTc is one of the generator-produced radioisotopes oftenconsidered as the ‘work-horse’ of diagnostic nuclear medicine owingto its ideal nuclear decay characteristics. 99mTc is usually obtainedfrom a 99Mo/99mTc generator, in which 99Mo is loaded onto analumina column. The daughter product 99mTc as TcO4

� can easily beeluted from the generator column using 0.9% NaCl solution. With its

ll rights reserved.

ready availability and favorable nuclear properties, 99mTc is also anattractive radioisotope of choice for radiotracer applications in theindustrial sector and has been extensively studied by several groups(Berne and Thereska, 2004; Hughes et al., 2004; Thyn and Zitny,2004; Borroto et al., 2003; Bandeira et al., 2002; Wolterbeek and vander Meer, 2002; Kantzas et al., 2000; Perret et al., 2000; Charlton,1997; Fauquex et al., 1983). The column material of nearly allcommercially available 99Mo/99mTc generators is alumina owing toits ready availability, high degree of specificity and proven perfor-mance (Ram et al., 2009; Hou et al., 2007; Knapp and Mirzadeh,1994; Bremer, 1987). In spite of its extensive use in medicalgenerators over years, small particle sizes of commercially availablealumina sorbent emerged as the primary obstacle against itsapplication in industrial generator. Frequent transportation ofgenerator to multiple locations for field study can result in distur-bance of the regular packing of the alumina in the column. This inturn can lead to bleeding of fines, variability in product purity, non-reproducible yields, fluctuating flow, etc. Therefore, concern has beenexpressed regarding their performance in operation under harshindustrial conditions. This potential weakness substantially limits theapplicability of fine alumina powder in the industrial generatorsystems and prompted us to search for alternative forms of alumina.

Alumina as microspheres appears to be an ideal option tocircumvent these drawbacks owing to its excellent mechanicalstrength and high density. Alumina microspheres have been reported

A. Dash et al. / Applied Radiation and Isotopes 70 (2012) 51–5852

to be effective for the sorption and desorption of molybdenum(Carvalho and Abrao, 1997) due to the presence of reactive surface.There have been several approaches for making such microspheres(Hyodo et al., 2005; Kou et al., 2005; Sze!pvolgyi and Ka!roly, 2004;Kato et al., 2003; Takayuki et al., 2002; Pius et al., 1999; Chatterjeeet al., 1998). Out of these, the ‘‘sol–gel’’ approach is the mostcommonly used technique. This is based on the preparation of aconcentrated colloidal sol of the aluminum hydroxide and itstransformation into a semi-rigid gel followed by heating. A novelsynthetic approach has been developed in our institution for thepreparation of alumina microspheres using internal gelation process(Pillai et al., 2001). In this communication, we attempted to inves-tigate the application of this material towards the development of99Mo/99mTc industrial chromatographic generator. We report herethe successful demonstration of an industrial 99Mo/99mTc generatorsystem using alumina microspheres to obtain radionuclidically,radiochemically and chemically pure 99mTc in both organicand aqueous media for their possible use in industrial radiotracerinvestigations.

2. Experimental

2.1. Materials

Reagents such as nitric acid, aluminum nitrate, carbon tetra-chloride (CCl4), urea, hexamethylenetetramine (HMTA) ,etc. wereof analytical grade and were procured from E. Merck, Darmstadt,Germany. Paper chromatography strips and fibrous cellulose(Whatman CF11) for XRF measurement were obtained fromM/s. Whatman, UK. Flexible silica gel plates (coating thickness0.25 mm) were from J.T. Baker Chemical Company, USA.

99Mo as sodium molybdate in 2 M NaOH (150 mg of Mo/mL,concentration: 1.11–2.22 GBq/mL (30–60 mCi/mL)), available withthe Radichemicals Section of our Division was used for the prepara-tion of industrial generator. For tracer experiments, molybdenumsolutions were spiked with fission-produced 99Mo (specific activity�104 Ci/g) obtained from Board of Radiation and Isotope Technol-ogy (BRIT), India.

2.2. Instruments

A mechanical wrist-action shaker (Secor, India) was used forbatch equilibrium studies. A HPGe Multichannel analyzer, coaxialphoton detector system, Canberra Eurisys, France with a 0.5 keVresolution, and an energy range from 1.8 keV to 2 MeV was usedfor analysis of 99Mo in the presence of 99mTc and also forquantitative estimation. The radioisotope levels were determinedby quantification of the 140 and 740 keV photo peaks correspond-ing to 99mTc and 99Mo, respectively. The trace level of metalcontaminations was estimated using Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-ES JY-238, Emission HoribaGroup, France). Energy Dispersive X-ray fluorescence Spectro-meter (Model no.: EX-M3600M of Xenemetrix Inc., Israel) wasused to measure the intensity of Mo Ka X-rays. X-ray diffractionmeasurements (101–701) were carried on the powder, usingmonochromatized Cu-Ka radiation on a Philips X-ray diffract-ometer, Model PW 1927. The XRF spectrometer is equipped witha Rh target X-ray tube (50 KV, 0.01–4 mA) and high resolutionSi(Li) detector. The surface area and the pore volume analysiswere carried out by the standard BET (Brunauer et al., 1938)technique and BJH method (Barrett et al., 1951) on a ‘‘Sorpto-matic-1990 Analyzer’’, procured from M/s C.E. Instruments, Italy.Fourier Transform Infrared (FT-IR) spectra of the synthesizedsorbent were recorded in a JASCO FT/IR-420 spectrometer.Density of the microspheres was determined from the Archimedes’

principle using glass specific gravity bottles. All the glass containersused in this investigation were acid-washed, rinsed with deionizedwater and dried in a clean oven.

2.3. Preparation of alumina microspheres

The alumina microspheres were prepared as per the reportedprocedure (Pillai et al., 2001). In brief, a broth solution containing1.4 M aluminum nitrate, 1.54 M urea and 1.54 M hexamethyle-netetramine was prepared by mixing them at a temperature of5 1C. The droplets of this broth were passed through hot siliconeoil at 95 1C, resulting in the formation of a gel. The spheres wereseparated from the oil, degreased with carbon tetrachloride (CCl4)and then washed thoroughly with ammonia solution (2 M) toremove the chemical impurities that might have percolated insidethe spheres. The spheres were dried in an air oven at 100 1C. Theair-dried microspheres were sintered at 700 1C for 5 h in afurnace, for making them insoluble.

2.4. Chemical stability

The chemical stability of the sorbent was assessed in severalmineral acids and bases, such as HCl, HNO3, NaOH and NH4OH asper the reported procedure (Chakravarty et al., 2009).

2.5. Measurement of distribution ratio (Kd)

Distribution ratios (Kd) were determined at different pHranging from 0 to 8, using 99Mo radiotracer and following thereported procedure (Chakravarty et al., 2010). The distributionratio (Kd) was calculated using the relationship:

Kd ¼ðAi-AeqÞV

Aeq m

where Ai is the initial radioactivity per mL of the solution, Aeq isthe activity per mL of the solution at equilibrium, V is the solutionvolume (mL) and m is the mass of the alumina microspheres (g).

2.6. Sorption capacity of alumina microspheres

2.6.1. Static 99Mo loading capacity

The ion exchange capacity of the alumina microspheres forMo as MoO-2

4 was determined at different pH values ranging from1 to 8 by batch-equilibration method, following the methodreported by us (Chakravarty et al., 2010). The capacity of aluminamicrospheres for adsorption of 99Mo was calculated using theexpression:

Capacity¼ðAi�AeÞ V

m

where, Ai and Ae represented initial and equilibration radio-activity of Mo, respectively, V was the volume of solution and m

was the mass (g) of the alumina microspheres.In order to study the effect of temperature on the 99Mo uptake,

capacity determination studies were carried out at differenttemperatures by immersing the reaction mixtures in a bathmaintained at a particular temperature.

2.6.2. X-ray fluorescence (XRF) studies

For verification of the Mo capacity data on alumina micro-spheres, another set of batch experiments were carried out usingsynthetic feed solution maintained at pH 3 and at room tempera-ture. The amount of Mo adsorbed on the alumina microsphereswas determined by Energy Dispersive X-Ray Fluorescence(EDXRF) technique.

Fig. 1. Pore size distribution of alumina microspheres.

A. Dash et al. / Applied Radiation and Isotopes 70 (2012) 51–58 53

2.6.2.1. Preparation of calibration standards. For each standard, 2 gof very pure microcrystalline cellulose was mixed with varyingquantities of sodium molybdate to obtain standards with 0.6–4.9%Mo by weight. This mixture was ground thoroughly to achieveuniformly small grain size. 1 g of the mixture was taken andpelletized. Six standards (as pellets) were prepared in duplicate.

2.6.2.2. Preparation of the samples. The Mo adsorbed in aluminamicrospheres were mixed with microcrystalline cellulose powder(�1 g), grounded thoroughly and then pelletized. Each pellet wasweighed and subjected to measurement. The optimum excitationparameters for measurement of Mo Ka X-rays were finalized byvarying the current and potential of the tube so as to getmaximum signal to background ratio and optimum detectordead time. Data acquisition and processing was carried outusing personal computer based 2 K multichannel analyzer(MCA) and software. The Ka analytical lines and backgroundintensities (counts s�1) were measured on both sides of the disksand the results were averaged.

2.6.3. Determination of breakthrough pattern and dynamic

adsorption capacity

Column experiments were carried out to study the break-through pattern and dynamic sorption capacity using thereported procedure (Chakravarty et al., 2010).

2.7. Development of 99Mo/99mTc generator

For the preparation of a typical 99Mo/99mTc generator, aborosilicate glass column [20 cm (l)�1.5 cm (f)] containingsintered G2 disk at the bottom was packed with 10 g of aluminamicrospheres (preconditioned with 0.001 M HNO3) in a leadshield. The column was then loaded with 1.85 GBq (50 mCi) of99Mo solution by passing 99MoO4

2� solution (at pH 3) through thecolumn. The specific activity of the 99Mo used was about 11.1 GBq(0.3 Ci)/g. Therefore, 1.85 GBq (50 mCi) of 99Mo corresponds to0.166 g of Mo. The generator column was washed by passing100 mL of 0.9% NaCl solution. After allowing growth of 99mTc, thegenerator was eluted with 10 mL of acetone or 0.9% NaCl solution.

2.8. Quality control of 99mTc eluate

2.8.1. Radionuclidic purity

Radionuclidic purity measurements were made using a cali-brated HPGe detector. The 99Mo contamination level in 99mTc wasquantified by allowing the 99mTc samples to decay for 2 days andthen measuring the 181 keV g-ray peak, corresponding to emis-sion from 99Mo contaminant. Further, the radionuclidic purity of99mTc was evaluated by the determination of its half-life.

2.8.2. Radiochemical purity

To evaluate the radiochemical purity of 99mTcO4� , 2 mL of

activity was applied on paper chromatographic strips (Whatman12 cm�1 cm) at 1.5 cm from the lower end. The strips weredeveloped in 85% methanol solution. The strip was air dried andthe distribution of activity was measured using a paper chroma-tography scanner.

2.8.3. Chemical purity

In order to determine the presence of Al3þ ions contaminatingthe 99mTc product (chemical impurities), the 99mTc samples wereallowed to decay for 10 days. The presence of trace level ofAl3þ ion contamination in the decayed samples was determinedby Inductively Coupled Plasma-Atomic Emission Spectroscopy(ICP-AES).

2.9. Recovery of 99Mo from the spent generator

The spent generator was washed with saline, and the 99Mo wasdesorbed with 5 M NaOH solution containing H2O2 (15 mL of 5 MNaOH solutionþ1 mL of 30% H2O2) as per the reported method(Mushtaq, 1995). The flow rate of the eluent was �0.5 mL/min. Theeluate was collected as 1 mL aliquots throughout the elution, andeach sample was counted for gamma activity. Then, all the fractionswere pooled together and the total activity of 99Mo eluted wasdetermined in a HPGe detector. For the regeneration of the column,it was washed with 100 mL of deionized water and conditioned atpH 3 by passing 0.001 N HNO3 solution.

3. Results

3.1. Preparation of the alumina microspheres

Several batches of alumina microspheres could be prepared bysol–gel method. The microspheres were found to be of uniformsizes, mostly spherical in morphology and contained very littlebroken particles. The gelated spheres were dried and calcined at700 1C at controlled heating rate so that the spheres do not crackdue to sudden decomposition of the organic dehydrating agent.During calcination, the trapped liquid, if any, vaporizes, leads todensification of the structure and the material becomes mechani-cally strong. Under such conditions, formation of solid microspherestakes place and the spheres develop porosity.

3.2. Structural characterization

The density of the alumina microspheres were in the range of1.5–1.9 g/cm3. The microspheres showed high packing density inthe column and exhibited free flow of liquid. The surface area ofthe alumina measured by standard BET technique was found outto be 175 m2 g�1. The pore size distribution of alumina micro-spheres were studied based on the BJH theory (Barrett et al.,1951) and the result obtained is depicted in Fig. 1. As seen fromthe figure, the pores are in the range of 20–200 A in sizes withpredominant pore size 20–30 A and average pore size of 55 A.This led us to the inference that the material obtained was

Table 3Effect of temperature on the static adsorption

capacity of alumina microspheres.

Temperature K (1C) Capacity (mg/g)

298 (25) 45

313 (40) 40

323 (50) 32

333 (60) 18

343 (70) 15

353 (80) 13

A. Dash et al. / Applied Radiation and Isotopes 70 (2012) 51–5854

mesoporous and the long-range mesopores are distributedthroughout the structure. The pore volume of the material wasin the range of 0.30–0.32 cm3/g.

3.3. Stability of the alumina microspheres

It was observed that alumina microspheres were insoluble inwater, dilute mineral acids and alkalis as o10 ppm level of Alions were detected in the filtrate when analyzed by ICP-AES. Thischaracteristic shows that the sorbent can be safely used for thepreparation of 99Mo/99mTc generator.

3.4. Distribution ratio (Kd)

It was observed that the selectivity of alumina microspheresfor MoO4

2� ions, as measured in terms of the Kd values of theseions, is strongly affected by the pH of the solution (Table 1). Theresults demonstrated that selectivity of 99Mo on this sorbent wasmaximum at �pH 3.

3.5. Sorption capacity of alumina microspheres

The sorption capacity of the sorbent was determined bothunder static and dynamic conditions.

3.5.1. Static 99Mo loading capacity

3.5.1.1. Static sorption capacity as a function of pH. The static loadingcapacity of 99Mo at different pH values ranging from 1 to 8 areshown in Table 2. The results show that the sorbent adsorbs 99Moover a wide range of pH and the maximum adsorption of 99Mo takesplace at �pH 3, which is in accordance with the earlier observationregarding Kd.

3.5.1.2. Static sorption capacity as a function of temperature. Thecapacity of the sorbent at different temperatures is shown inTable 3. It was observed that the temperature had a stronginfluence on the static adsorption capacity, which decreases

Table 1Variation of distribution ratio (Kd) of 99MoO4

2� ions

with pH.

pH Kd

0 8.3

1 33.2

2 38.3

3 95.1

4 49.1

5 40.5

6 29.2

7 18.7

8 16.2

Table 2Variation of static adsorption capacity with pH.

pH Capacity (mg/g)

1 26

2 42

3 46

4 39

5 28

6 30

7 12

8 11

with increasing temperature, probably due to the enthalpy ofadsorption. The ambient temperature of �298 K (25 oC) wasconsidered the best for practical applications.

3.5.1.3. Static 99Mo loading capacity by EDXRF method. The EDXRFspectrum of the Mo standard prepared is shown in Fig. 2. It is seenthat the intensity of Ka X-ray of Mo is more than that of Kb X-ray.Therefore the intensity of Ka X-ray was employed for quantifica-tion of Mo in all the samples. The procedure employed for thepreparation of synthetic standards using cellulose was satisfactoryand provided a simple way of preparing reliable calibration curve.The homogeneity of the standard samples was evaluated by takingtwo XRF scans for Mo on both sides of the pellets. The differencebetween the XRF readings between the two sides of the pressedpellet was less than 5%. A calibration graph was used to calculatethe concentrations of the Mo adsorbed by the aluminamicrospheres. Fig. 3 shows the EDXRF spectra of Mo-adsorbedalumina microspheres. The measured concentrations of Mo inalumina microspheres are depicted in Table 4. It showed thataverage capacity of the sorbent is 44.8 mg/g, which is close to thevalue obtained by radiometric technique.

3.5.2. Dynamic 99Mo loading capacity

The breakthrough profile of 99Mo developed at pH 3 is shownin Fig. 4. The breakthrough capacity of the sorbent was found outbe �15 mg Mo/g.

3.6. Process demonstration run

The operation of two 99Mo/99mTc generators, each of 1.85 GBq(50 mCi), were subjected to test for a period of 1 week. One of thegenerators was eluted with 0.9% NaCl solution to avail 99mTc inaqueous medium and the other generator was eluted withacetone in order to obtain 99mTc in organic medium. The perfor-mances of these generators in terms of 99mTc yield are shown inFig. 5. It can be seen from the figure that the elution yields of99mTc from the generators were always 480%, over this period oftime. The yield and flow characteristics of the column remainedunchanged after prolonged use for 1 week, with elution every day.The elution profiles of the generators (Fig. 6) were quite sharp andhigh radioactive concentration of 99mTc could be obtained.

3.7. Quality control of 99mTc

3.7.1. Radionuclidic purity of 99mTc

The purity of 99mTc was evaluated by gamma spectrometryusing a HPGe detector coupled with a multichannel analyzer. Fig. 7shows the gamma spectra of feed 99Mo and 99mTc immediatelyafter separation. The absence of any photo-peak corresponding togamma-energies due to 99Mo in the separated 99mTc samplesdemonstrated that the 99mTc was obtained in a fairly pure form.The trace amount of 99Mo impurity present in the 99mTc eluate wasquantified by gamma spectrometric analysis of decayed 99mTc

Fig. 2. EDXRF spectrum of standard Mo.

Fig. 3. EDXRF spectra of Mo-adsorbed alumina microspheres.

Table 4Capacity of the sorbent obtained by EDXRF method.

Pelletno.

Weightofpellet(g)

Weightofsamplein thepellet (g)

Intensity(CPS)

Amountof Mopresent(mg)

Amount ofMo presentper gram ofsorbent (mg)

Averagecapacityof thesorbent(mg/g)

1 0.9664 0.0798 987 3.577 45 44.8

2 0.9329 0.1294 1521 5.888 45.5

3 0.9522 0.2051 2231 9.026 44

00.0

0.2

0.4

0.6

0.8

1.0Amount of sorbent = 1 gBreakthrough capacity (C/C0 0.1) = 15 mg/gTotal capacity (C/C0 0.9) = 40 mg/g

C/C

0

Amount of Mo (mg)10 20 30 40 50

Fig. 4. Breakthrough profile of 99Mo.

A. Dash et al. / Applied Radiation and Isotopes 70 (2012) 51–58 55

samples and it was found that the level of 99Mo impurity in 99mTcwas o0.1%. The half life of 99mTc as calculated from its decayprofile was 6.170.3 h (n¼5), which is quite close to thetheoretical value.

The amounts of 99Mo impurity present in the 99mTc eluatesduring the process demonstration runs with 0.9% NaCl solutionand acetone are shown in the Fig. 8. The level of 99Mo impuritypresent in the 99mTc eluate due to its breakthrough from thecolumn was found to be o0.1%. Thus, 99mTc could be availedfrom both the generators with adequately high radionuclidicpurity, consistently over a period of 1 week.

3.7.2. Radiochemical purity

Radiochemical purity is an important parameter necessary toensure the chemical form in which 99mTc is present in the eluate.In 85% methanol, 99mTcO4

� migrates towards the solvent front andany hydrolyzed 99mTc (as 99mTcO2) if present remains at the pointof spotting. Fig. 9 depicts a typical paper chromatography patternof 99mTc availed from the generator. It was observed that 499% of

99mTc was present in 99mTcO4� form, when eluted with either 0.9%

NaCl solution or acetone. Presence, of 99mTc in pertechnate ionform ensures its potential for use in flow rate measurements, asany hydrolyzed 99mTc (TcO2) if present may get precipitated.

3.7.3. Chemical purity

The presence of chemical impurities in the form of bleeding ofthe column matrix hampers the labeling efficacy of 99mTc for itseffective use as radiotracer and is thus an essential parameter to

10

20

40

60

80

100

Elut

ion

yiel

d of

99m

Tc (%

)

Time of elution (days)

10

20

40

60

80

100

Elut

ion

yiel

d of

99m

Tc (%

)

Time of elution (days)

2 3 4 5 6

2 3 4 5 6

Fig. 5. Performance of the 99Mo/99mTc generators using (a) 0.9% NaCl solution and

(b) acetone as eluents.

00

5

10

15

20

25

30

Yiel

d of

99m

Tc (%

)

Volume of 0.9% NaCl solution (mL)

0

5

10

15

20

25

Yiel

d of

99m

Tc (%

)

Volume of acetone (mL)

1 2 3 4 5 6 7 8 9 10

0 1 2 3 4 5 6 7 8 9 10

Fig. 6. Elution profiles of 99mTc using (a) 0.9% NaCl solution and (b) acetone as

eluents.

A. Dash et al. / Applied Radiation and Isotopes 70 (2012) 51–5856

be determined. This was analyzed by ICP-AES and the level of Alions present was found to be o0.1 ppm. It is clear that negligibleamount of Al ion contamination was present in the eluate.

3.8. Regeneration of the alumina column

When the activity of the 99Mo decreases below a certain value,it is no longer useful for industrial application and could not bereused or discarded without removing the sorbed 99Mo. Theabsorbed 99Mo from the exhausted column was recovered using3 M NaOH solution (15 mL NaOH solution þ1 mL 30% H2O2)adopting the procedure reported by Mushtaq (1995). The elutionbehavior of 99Mo, as followed by counting the residual radioactivity,from the column is shown in Fig. 10. It is seen that the recovery ofMo was quick and nearly all the Mo could be eluted out in the first4–5 mL of the eluent. At 3 M NaOH concentration, the sorbentdesorbed �94% of 99Mo. Freshly produced 99Mo could be re-loadedin the regenerated column and 99mTc could be eluted out under thesame conditions as described earlier.

4. Discussion

Alumina microspheres have the potential to maintain the integ-rity in a chromatographic column under harsh environmental

conditions and were therefore chosen for this application. Exhaustivesorption and elution properties were evaluated to understand theultimate sorption limits, elution behavior of 99mTc and regenerationof sorbent, in a specific set of experimental conditions. In order toreinforce the result on the capacity data, an additional study basedon XRF was carried out. We have chosen the EDXRF technique for thefollowing important reasons: (1) simplicity of sample preparation,(2) minimum manipulation, which reduces the possibility of con-tamination, and (3) speed, taking into account the number ofsamples. This result corroborates the data obtained by radiometrictechnique. Moreover, the use of multiple techniques increases thereliability of result.

Adsorption of 99Mo polyanions apparently took place insidethe meso and macro-pores of alumina microspheres. The aqueouschemistry of molybdenum has been well explored. There arevarious anionic species of molybdenum, varying with pH. AtpH46 the predominant species is MoO2�

4 , at pH 5–6, thepredominant species is Mo7O6�

24 and at pHo5 the speciesMo8O4�

28 predominates (Arino and Kramer, 1975). The aluminamoieties become positively charged at acidic pH and readilyadsorb the molybdenum polyanions in the pores under thiscondition due to the formation of stable heteropoly complexesof the type [AlMo6O24]9� (Molinski, 1982; Steigman, 1982). Thedecay of 99Mo to 99mTc is not accompanied by any serious

40002000010

100

1000

10000

778 keV: 99Mo

740 keV: 99Mo 181 keV: 99Mo

140 keV: 99mTc

Cou

nts

(log

scal

e)

Channel Number

400020000

10

100

1000

10000140 keV: 99mTc

Cou

nts

(log

scal

e)

Channel Number

Fig. 7. Gamma spectrum of (a) feed 99Mo and (b)separated 99mTc.

10.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

Rat

io o

f 99M

o to

99m

Tc (B

q/kB

q)

Elapsed time (days)

Acetone Saline

2 3 4 5 6 7

Fig. 8. Variation in the amount of 99Mo impurity present in the 99mTc eluate over

the period of 1 week.

0 20 40 60 80 100

TLC

mm0

10

20

30

40

50

60

70

80

90

100

110

Orig

in

Sub

stan

ce-0

01

Fig. 9. Paper chromatographic pattern of 99mTc.

00

10

20

30

40P

erc

en

tag

e o

f 99M

o e

lute

d

Volume of 3 M NaOH (mL)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Fig. 10. Elution profile of 99Mo from the spent generator column.

A. Dash et al. / Applied Radiation and Isotopes 70 (2012) 51–58 57

disruption of chemical bonds. 99Mo is retained on the sorbentmatrix as polymeric molybdate anions and gets transformed intopertechnetate ion (99mTcO4

�), which owing to the lower charges of–1 would in turn have weaker binding and hence easily displaced.Therefore 99mTc gets eluted easily with normal 0.9% NaCl oracetone. For selecting an appropriate aqueous eluting agent,

0.9% NaCl was the first choice because it has nearly neutral pH,very similar to that of water. Availability of 99mTc in acetone,which is soluble in hydrocarbon solvents enhances the scope ofusing the generator in oil and petroleum industries for radiotracerapplications. Acetone was able to enter inside the meso- andmacro-pores of alumina microsphere and displace 99mTcO4

�

(Mushtaq, 2003).The chromatographic column containing alumina micro-

spheres was validated under actual conditions to evaluate thebehavior of the system in the presence of intense radiationenvironment with the radiolytic products generated as a resultof radioactive 99Mo. Reproducible recovery of 99mTc was observedwith a yield 480%. The purity and elution yield of the 99mTcO�4remained nearly unchanged with long term operation.

When the activity of the 99Mo decreases below a certain value,the 99Mo/99mTc generator is no longer useful for industrialapplications. Molybdate ions could be released from the sorbentmatrix under alkaline condition due to the reversible nature ofthe interaction between these ions and alumina microspheres.This step is also important, if Mo recovery is needed in case theprocedure is adopted with enriched target. Moreover, aluminamicrospheres can also be used as a recyclable sorbent.

A. Dash et al. / Applied Radiation and Isotopes 70 (2012) 51–5858

While our work mainly focused on the demonstration of theutility of alumina microspheres for the preparation of 99Mo/99mTcindustrial generator using (n, g) 99Mo, the present concept can beextended to make medical generators. In such cases, use of fission99Mo is mandatory owing to the limited capacity of aluminamicrospheres. Additionally, use of pre-sterilized reagents,columns, connectors, tubing and vials for 99mTc collection areobligatory to provide sterility and apyrogenicity of the final 99mTceluates. Such strategy merits more detailed assessment.

From the study we observed three clear trends. First, aluminamicrospheres remain stable in the column without mechanicaland chemical degradation. This simply reflects the high toughnessof alumina microspheres prepared by sol–gel process. Secondly,alumina microspheres have higher capacity for 99Mo in thecomparison of commercial alumina, which is largely due to itshigh surface area, which in turn promotes loading of the availablesites with molybdate polyanions. The more rapid mass transfer of99Mo into the alumina microspheres led it to demonstrate ahigher effective capacity. Thirdly, process demonstration studiescarried out on 99Mo loaded alumina column clearly indicate thepotential of 0.9% NaCl as well as acetone for use as eluents toobtain 99mTc that can be used as industrial radiotracer.

5. Conclusion

We have developed a simple, convenient and efficient approachfor the preparation of industrial 99Mo/99mTc generator using alu-mina microsphere synthesized through a novel sol–gel process. Thistechnique is facile, versatile, efficient, highly selective, gives repro-ducible results, offers high overall yield of 99mTc and is attractive forradiotracer applications. Further work is currently underway tovalidate this radionuclide generator for radiotracer application inindustries.

Acknowledgments

The work was initiated as a part of an IAEA Coordinated ResearchProject on ‘Evaluation and Validation of Radionuclide Generators-based Radiotracers for Industrial Applications’. The authors arehighly grateful to Dr. V. Venugopal, Director, RC&I Group, BARC forhis continuous encouragement and support for this program.The authors wish to acknowledge Dr. S.K Aggarawal, Head, FuelChemistry Division and Dr. (Ms.) S. Ray, Head, Uranium ExtractionDivision of this center for providing their facilities for the prepara-tion of alumina microspheres and ICP analyses, respectively.

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