Separation of Clinical Grade 188Re from188W Using Polymer EmbeddedNanocrystalline Titania

Rubel Chakravarty, Ashutosh Dash&, Meera Venkatesh

Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085, India; E-Mail: adash@barc.gov.in

Received: 14 August 2008 / Revised: 15 January 2009 / Accepted: 16 February 2009

Abstract

Currently, 188Re is obtained from 188W/188Re chromatographic generator containing alu-mina which has a limited capacity (*80 mg Wg-1) for 188W. This results in high bolusvolumes of 188Re, which often needs to be concentrated before radiolabeling. We havedemonstrated the feasibility of using polymer embedded nano crystalline titania (TiP), a novelhigh capacity sorbent material (*300 mg Wg-1), for developing a 188W/188Re chro-matographic generator. A TiP based chromatographic 188W/188Re generator was devel-oped in which 188Re could be eluted with 0.9% saline solution. About 90% of the 188Re couldbe recovered in the first 4–5 mL of total activity with more than 80% yield. The purity of 188Reis adequate for clinical applications.

Keywords

Inductively plasma-atomic emission spectroscopyPolymer embedded nanocrystalline titania188W/188Re chromatographic generatorRadiochemical and radionuclidic purity

Introduction

There is a great deal of interest in the use

of 188Re (T½ = 16.9 h) for various ther-

apeutic applications including bone pain

palliation, synovectomy, and intravascu-

lar radiation therapy (IVRT) [1–9] due

to its attractive properties such as emis-

sion of high energy beta particles

(Eb,max = 2.118 MeV) and low (15%)

emission of a 155 keV c-ray, suitable formonitoring and dosimetry. IVRT using a

balloon filled with 188Re-solutions has

been demonstrated to be a simple and

effective modality of treatment [7, 9, 10].

Further, being analogous to Tc, the

chemistry of Re would be similar and

hence would be interesting to study as a

pair with 99mTc. Although (n,c) reactionof 187Re (enriched) would yield 188Re, it is

generally obtained from the beta-decay of188W, since high specific activity of 188Re

is ideal for therapeutic applications [1–8].188W is produced by double neutron

capture on enriched 186W oxide [11–14].

Due to the double neutron capture pro-

cess with low absorption cross sections

[186W(n,c)187W (r = 37.9 ± 0.6 b);187W(n,c)188W (r = 64 ± 10 b) and the

appreciably long half-life of 188W

(69.2 days), relatively long irradiation

periods are required even for the pro-

duction of 188W of modest specific activ-

ity. However, 188W from high flux

reactors canbe used tomake a 188W/188Re

generator to obtain ‘no carrier added188Re’. Most of the commercially avail-

able 188W/188Re generators are akin to the99Mo/99mTc generators using alumina

columns, where tungsten is retained on

the alumina column and 188Re is eluted

with 0.9% NaCl solution [11, 15–20].

Perego et al. [21] have examined the

tungsten adsorption capacity of a variety

of alumina powders and prepared a

130 GBq 188W/188Re generator using

alumina as sorbent with a capacity of

80 mg Wg-1. Using this generator it was

possible to elute 188Re with 80% yield

having a radioactive concentration of

14 GBq mL-1. But, unlike the 99Mo/99m

Tc alumina column generators, in the case

of 188W/188Re, the 188Reobtained is dilute

with low radioactivity concentration, due

to the low specific activity of 188W.

DOI: 10.1365/s10337-009-1070-7� 2009 Vieweg+Teubner | GWV Fachverlage GmbH

Original

Although most commercial188W/188Re generators are based on

alumina as sorbent, alternative pathways

such as 188W/188Re gel generator system

based on matrices such as zirconium

tungstate or titanium tungstate which

are isopolytungstates [22, 23] have also

been exploited. The development of

alternative sorbents for 188W/188Re gen-

erator, with higher capacity for W such

as gel metal oxide composite, hydroxy-

apatite and polymeric zirconium com-

pound (PZC) [24–27] have also been

investigated. However, these materials

have yet to reach the commercial stage

for clinical applications.

In recent years, the nano sized mate-

rials have been avidly explored by scien-

tists for various applications owing to

their extremely small size, large specific

surface area and higher availability of

reactive surface sites [28]. Due to the large

surface areas and hence the presence of

highpercent of the atomson the surface of

nanomaterials, they possess unique

properties that are not found in corre-

sponding bulk materials. The surface

atomsof nanoparticulatemetal oxides are

unsaturated, exhibit intrinsic surface

reactivity and can strongly adsorb metal

ions in solution. The potential of such

nanomaterials as new generation of sor-

bents in the chromatographic separation

of metal ions [29–31] has been exploited.

However, researches about the prepara-

tion of radionuclidic generator using

nanoparticles are seldom reported. In

order to tap the potential of nanomateri-

als as a sorbent in the relatively unex-

plored field, we have reported the

synthesis and characterization of a noble

sorbent, polymer embedded nano crys-

talline titania (TiP) for its possible appli-

cation in the preparation of 99Mo/99mTc

generator [32]. As a logical extension, we

evaluated the suitability of this high

capacity andhigh selectivity sorbent (TiP)

for the preparation of 188W/188Re gener-

ator.We felt that the long half-life of 188W

in comparison to that of 99Mo (66 h),

could be an advantageous attribute in this

endeavor of preparing an 188W/188Re

generator with TiP. Preparation of TiP

based 188W/188Re generator and assessing

the 188Re eluted with normal saline for

radiopharmaceuticals preparations are

addressed in this communication.

Experimental

Materials

Reagents such as hydrochloric acid,

ammonium hydroxide, etc. were of ana-

lytical grade and were procured from SD

Fine Chemicals, Mumbai, India or BDH

(India). Titanium tetrachloride (99.9%)

and isopropyl alcohol (AR grade) were

obtained from E. Merck, Mumbai,

India. Stannous chloride andDMSAwere

obtained from Sigma (St. Louis, MO,

USA). Na2H2HEDP was from Sigma.

Paper chromatography strips were pur-

chased from Whatman, UK. Flexible

silica plates (coating thickness 0.25 mm)

were from J.T. Baker, USA.

Tungsten-188 (specific activity

159 GBq g-1) as sodium (188W) tung-

state was procured from the State Sci-

entific Centre of Russia Research

Institute of Atomic Reactors (PSUE) in

Dmitrovgrad, Russia, through an IAEA

coordinated research project.

Equipment

Gamma spectrometry of 188Re, was per-

formed by using a NaI (Tl) scintillation

counter (50–150 keV). An HPGe multi-

channel analyzer, coaxial photondetector

system, Canberra Eurisys, France with a

0.5 keV resolution and range from 1.8 to

2 MeV was used for analysis of 188W in

the presence of 188Re and also for quan-

titative estimation. The radioisotope lev-

els were determined by quantification of

the 188Re 155 keV (15%) and 188W

291 keV (0.4%) photo peaks. The zeta-

potential of the nano particles were mea-

sured using a Zetasizer Nano ZS/

ZEN3600, Malvern Instruments, UK.

The chemical analysis for the determina-

tionof trace level ofmetal contaminations

was by inductively coupled plasma-

atomic emission spectroscopy (ICP-AES

JY-238, Emission Horiba Group,

France).

Synthesis of TiP

TiP was synthesised in situ by the reac-

tion of TiCl4 and isopropyl alcohol in 2:1

stoichiometric ratio, as reported by us

earlier [32].

Chemical Stability

The chemical stability of the TiP sorbent

prepared was assessed in several mineral

acids and bases, such as HCl, HNO3,

NaOH and NH4OH. A weighed amount

of the sorbent material (1 g) was placed

in 50 mL solvent of interest and kept for

24 h with continuous shaking at room

temperature. Subsequently it was filtered

and the level of Ti metal ions in the fil-

trate was determined by ICP-AES.

Determination of theDistribution Ratiot (Kd)

Distribution ratios (Kd) of tungsten and

rhenium for the TiP matrix were mea-

sured at different pH, using 188W and188Re radiotracers. In each experiment,

200 mg of sorbent was suspended in

20 mL solution containing *10-3 M

radioactive metal ion in a 50 mL stop-

pered conical flask, shaken in a wrist arm

mechanical shaker for 1 h at 25 �C and

then filtered. The activities of the solu-

tion before and after equilibration were

measured in a well type NaI (Tl) counter

using appropriate window ranges (100–

200 keV for 188Re and 250–350 keV for188W). The distribution ratios were cal-

culated using the following expression

Kd ¼ðAi � AeqÞV

Aeqm

whereAi is the initial total radioactivity of

1 mL the solution, Aeq is the unadsorbed

activity in 1 mL of the solution at equi-

librium, V is the solution volume (cm3)

and m is the mass (g) of the adsorbent.

Determination of the Timeof Equilibration

In order to study the time dependence of

sorption of 188W onto TiP, distribution

ratio (Kd) of188W in 0.1 M HNO3 was

determined at different time intervals, as

described above. The Kd values (mean of

three experiments) were taken as an

indication of the progress of the

adsorption process. The time when Kd

remained unchanged, was taken as the

indication of the attainment of equilib-

rium.

Original

Determination of ZetaPotential

A weighed amount of the sorbent (5 mg)

was added to 50 mL of de-ionized water

and the pH of the suspension was ad-

justed using HClO4 and HNO3. Zeta-

potential of the suspensions at different

pH was measured with a combination of

laser doppler velocimetry and phase

analysis light scattering (PALS). Smolu-

chowsky constant F (Ka) of 1.5 was used

to calculate zeta-potential values from

the electrophoretic mobility. All mea-

surements were carried out at 25 �C in

triplicate.

Capacity Measurement

The ion exchange capacity of the

adsorbent TiP for W was determined by

batch equilibration method. An accu-

rately weighed amount of TiP (0.5 g)

was taken in different glass stoppered

conical flasks and equilibrated with

50 mL of sodium tungstate solution

(10 mg of Wm L-1) spiked with

*10 lCi (370 KBq) of 188W for about

1 h at room temperature. At the end, the

contents were filtered through filter pa-

per. The activities of 188W in the solution

before and after absorption were esti-

mated by using a HPGe detector coupled

to a multichannel analyzer, by measur-

ing the counts at 291 keV peak corre-

sponding to 188W. All measurements

were carried out at 25 �C in triplicate.

The capacity was calculated using the

following expression

Capacity ¼ ðC0 � CeÞVm

where, C0 and Ce represented initial and

equilibration concentration of W,

respectively,Vwas the volume of solution

and m was the mass (g) of the adsorbent.

Determination ofBreakthrough Pattern andDynamic Adsorption Capacity

In order to estimate the W absorption

capacity under dynamic conditions, a

borosilicate glass column of 15 cm 9

0.4 cm (i.d) with a sintered disc (G2) at

the bottom was packed with 0.5 g of

the synthesized adsorbent. After the

column was conditioned with 0.01 M

HNO3, sodium tungstate solution

(10 mg W mL-1), spiked with 188W tra-

cer (37 KBq mL-1) was allowed to pass

through the column at a rate of

0.25 mL min-1. 1 mL of this solution

was kept as reference (C0). The effluent

was collected in fractions of 1 mL ali-

quots (C). The 188W activity in the ref-

erence (C0) and effluent fractions were

determined by measuring the 291 keV

c-ray peak of 188W in a HPGe detector.

The ratio of the count rate ‘C’ of each

1 mL effluent to the count rate ‘C0’ of

1 mL of the original feed W solution was

taken as the parameter to follow the

adsorption pattern.

Preparation of 188W/188ReGenerator

A borosilicate glass column of

15 cm 9 0.4 cm (i.d.) with a sintered

disc (G2) at the bottom was packed with

2 g of TiP and then loaded with

1.85 GBq (50 mCi) of 188W solution in a

lead shield. Subsequently, after allowing

adequate time (2–3 days) for the 188Re

build-up, the column was eluted with

0.9% NaCl solution at a flow rate of

0.5 mL min-1 to study the elution

behaviour of 188Re from the column.

The eluate was collected as 1 mL ali-

quots and each fraction was counted for188Re gamma activity. The performance

of the generator was evaluated for

*6 months at ambient temperature.

Quality Control of 188Re Eluate

Radionuclidic Purity

Radionuclidic purity of the samples was

assessed using a calibrated HPGe detec-

tor coupled to a multichannel analyzer.

The 188W present in 188Re eventually

decays and forms an equilibrium mixture

of 188W/188Re, which can be quantified

by measuring the 188Re present. The188W contamination level in 188Re was

quantified by allowing the separated188Re samples to decay for 15 days and

then measuring the 155 keV c-ray peak,

corresponding to emission from 188Re

daughter which in turn corresponds to

the level of 188W contaminant. The re-

sults were further confirmed by counting

the decayed samples for a long time (6 h)

and measuring, the 291 keV c-ray peak

of 188W.

Radiochemical Purity

To evaluate the radiochemical purity of188ReO4

-, 5 lL of activity was applied

on paper chromatographic strips

(Whatman 12 cm 9 1 cm) at 1.5 cm

from the lower end. The strips were

developed in 0.9% saline. After chro-

matography, the paper strip was dried,

cut in to 1 cm segments, placed in test

tubes and counted in a NaI (Tl) scintil-

lation counter.

Chemical Purity

In order to determine the presence of Ti

ions in the 188Re product as a chemical

impurity, the 188Re samples were

allowed to decay for 20 days. The trace

levels of Ti metal contamination in the

decayed samples were determined by

ICP-AES using a linear calibration

graph of five reference solutions in the

concentration range of 0.5–10 ng mL-1

of titanium.

Labeling Efficacy

188Re from the generator was used to

prepare complexes of dimercaptosucci-

nic acid (DMSA) and hydroxyethylidene

diphosphonate (HEDP) as per the

reported procedures [33–36].

Recovery of Enriched 186Wfrom the Spent Generator

The spent generator was washed with

saline, and the W was desorbed with 5 M

NaOH solution containing H2O2 (15 mL

of 5 M NaOH solution + 1 mL of 30%

H2O2) at a flow rate of *0.5 mL min-1

as per the reported method adopted for

alumina [37]. The eluate was collected as

1 mL aliquots and each sample was

counted for gamma activity in a HPGe

detector. Then, all the fractions were

pooled together and the total activity of188W eluted was determined.

Original

Simulated Study for theSeparation of Re from a W/ReCarrier Added Solution,Equivalent to *37 GBq(1 Ci)of 188W and 188Re

The effects of macroscopic amounts of

tungsten on the efficiency of chromato-

graphic separation of 188Re using TiP

were investigated by using W/Re mixture

containing inactive carrier W and Re

equivalent to *37 GBq (1 Ci) 188W in

equilibrium with 188Re. The mixture

was spiked with an equilibrium mixture

of 188W/188Re containing 3.7 MBq

(100 lCi) of 188Re. This simulated solu-

tion was prepared by dissolving 292 mg

of WO3 [equivalent to 37 GBq (1 Ci) of188W at 159 GBq/g of 188W specific

activity] and 1.45 lg (equivalent to

37 GBq of 188Re) of ammonium perr-

hennate in 2 M NaOH. The resultant

solution was evaporated to dryness and

then reconstituted with 0.01 M HNO3

solution. The mixture was loaded in a

borosilicate glass column [15 cm 9

0.4 cm (i.d.)] containing 2.5 g of TiP

adopting the procedure outlined above.188Re was eluted with 5 mL of 0.9%

saline solution under the same condi-

tions as in the previous studies. The

efficiency of 188Re elution and the 188W

breakthrough were determined.

Results

The goal of the present study was to

evaluate the merits of the material (TiP),

developed by us, in the preparation

of 188W/188Re generator system. We

attempted to explore the possibility and

optimize the various process parameters

in order to achieve this objective.

It was observed that the material

(TiP) was insoluble in water, dilute

mineral acids and alkali (up to 4 M) as

<0.1 ppm level of Ti were detected in

the filtrate when analyzed by ICP-AES.

It is clear that only a negligible amount

of sorbent dissolved. There was no tur-

bidity when the sorbent was suspended

in water for 24 h. This characteristic

shows that the adsorbent can be safely

used for generator preparation.

Time Dependence ofAdsorption

The time dependence of the sorption of188W ions on TiP was measured in order

to determine the time required to attain

equilibrium. The plot of Kd versus time

is demonstrated in Fig. 1. As inferred

from the curve, a contact period of

45 min was maintained for all equilib-

rium tests.

Distribution Ratio (Kd)

The distribution ratio (Kd) results for188W and 188Re in TiP are summarized in

Table 1. It is apparent that for TiP, the

Kd values for W and Re are maximum at

around pH 2–3. The high Kd values for188W indicate that 188W could be effi-

ciently retained by the sorbent in 0.9%

NaCl, while the moderate Kd values for188Re in saline environment may not be

adequate for retention, resulting in its

easy elution.

Zeta Potential

The variation of zeta potential of TiP

with pH is illustrated in Table 2. The

zeta potential value is positive in the pH

range 1–6 and has a maximum around

pH 2. This indicates that in this pH

range, coulombic attraction can readily

take place, in conjunction with specific

chemical adsorption, between the sor-

bent and tungstate poly anions. This

property would help us to optimize the

loading condition of 188W.

0 10 20 30 40 50 60 700

20

40

60

80

100

120

140

160

180

200

220

Dis

trib

utio

n R

atio

(Kd)

Time (min)

Fig. 1. Variation of distribution ratio (Kd) with time

Table 1. Distribution ratios (Kd) of188W and

188Re in different media

S.No. Medium Kd

188W 188Re

1 pH 1 191 232 pH 2 244 613 pH 3 235 834 pH 4 195 565 pH 5 189 386 pH 6 175 467 pH 7 34 158 pH 8 22 39 0.9% NaCl 90 0.7

Table 2. Determination of zeta potential ofTiP as a function of pH

pH Zeta potential (mV)

1 36.6 ± 1.72 60.5 ± 2.13 46.1 ± 1.14 43.4 ± 1.65 44.0 ± 0.56 41.1 ± 1.87 -30.19 ± 0.98 -43.03 ± 1.2

(n = 3, ± indicates standard deviation)

Original

Static Adsorption Capacityof TiP

The results of the capacity determination

experiment by batch equilibrium meth-

od, indicated that the amount of W ad-

sorbed ranged from 325 to 328 mg g-1

of TiP at pH 3–6.

Dynamic Adsorption Capacityof TiP

The adsorbent TiP showed a strong

retention of 188W at pH 2 to 3 where

optimum Kd was realized. In order to

portray the adsorption behavior of 188W

in generator column bed containing TiP,

the breakthrough curve was developed at

pH * 2 and depicted in Fig. 2. The value

of C/C0 (ratio of 188W solution in the

effluent and 188W concentration in the

loading solution) indicates the fraction of188W coming out unadsorbed in the col-

umn. It was observed that the break-

through point was reached after 102 mg

of W per g of TiP (n = 3) was quantita-

tively retained by the column. The

capacity of the sorbent at C/C0 = 0.5 was

found out to be 174 mg ofW per g of TiP.

The saturation capacity was observed

to be 292 mg of W per g of TiP at

C/C0=0.9.However, itwas seen thatC/C0

remains at 0.9 even after passing 180 mL

of feed. This indicates slow retention of

the 188W input, which perhaps is accom-

modated in the inner sites of the particles

after the outer sites are saturated. Perhaps

after passing a large amount of 188W

solution, the static capacity of

*325 mg W per g of TiP could be

reached. But this is impractical in real

situations andoftenC/C0 of 0.5 is taken as

the practical limit. As expected, it was

observed that the dynamic capacity of the

sorbentwas less than the static capacity. It

was also observed that 188W was favor-

ably adsorbed on the column without

decreasing the column bed volume.

Preparation of 188W/188ReGenerator

In order to exploit the potential of TiP as

a column matrix for 188W/188Re genera-

tor, process demonstration run was

performed using 1.85 GBq (50 mCi)

activities of 188W/188Re and the elution

behavior of 188Re was studied. The

practical utility and separation capabil-

ity of 188Re by the sorbent material were

monitored, by following the elution

profile of the generator as shown in

Fig. 3.

It was observed that 188ReO4- eluted

out steadily with a yield >80% in a

sharp profile with *90% of the activity

eluted within the first 3–5 mL of normal

saline. The profiles were stable during

6 months of operation and the yields

varied within 10%.

Figure 4 summarizes the results of the

operation of the 188W/188Re generator

over a period of 4 months. It is seen that

the yield of 188Re was about 80–90% on

elution with normal saline solution and

the performance of the generator

remained consistent throughout.

Quality Control of 188Re Eluate

Radionuclidic Purity

The principal radionuclidic impurity

that is expected in the 188Re product is188W. Figure 5 summarizes the results of

the amount of 188W present in the eluate

0 20 40 60 80 100 120 140 160 180 200

0.0

0.2

0.4

0.6

0.8

1.0

Amount of TiP in the column = 500 mg

C/C

0

Amount of W (mg)

Fig. 2. Dynamic adsorption capacity of TiP for tungsten

0 1 2 3 4 5 6 7 8 9 100

10

20

30

40

50

Perc

enta

ge o

f 1

88R

e el

uted

Volume of 0.9% saline solution (mL)

Fig. 3. Elution profile of the generator

Original

with time. The level of 188W present in

the eluate was below 10-3% in different

batches, which is within the acceptable

limit [38] of 10-3%.

Radiochemical Purity

Paper chromatography (PC), developed

in saline could separate 188Re-perrhenate

from 188Re in other oxidation states. The

chromatographic pattern of 188Re eluate

is shown in Fig. 6. It is seen that 95–98%

of the 188Re activity was present as

perrhenate, which is within the pre-

scribed limits of �95% as perrhenate, as

per the British Pharmacopoeia [38].

Chemical Purity

The presence of Ti, possibly bleeding

from the column matrix (TiP) as ana-

lyzed by ICP-AES was as low as

(0.05 ± 0.01) ppm in the eluate. This we

believe is adequately low and the 188Re

product is suitable for radiopharmaceu-

tical preparations.

Labeling Efficacy

In order to examine the suitability of188ReO4

- for radiolabelling studies, it

was complexed with DMSA and HEDP.

In both cases, when TLC was performed

using acetone as solvent, the complex

remained at the point of application

(Fig. 7). Under identical conditions,188ReO4

- moved towards the solvent

front. However, if hydrolyzed rhenium

(188ReO2) is present, it will also remain

at the origin and hence an additional

quality control procedure of TLC in

saline was essential to estimate this

radiochemical impurity in the complex.

The TLC pattern, using 0.9% saline

solution as solvent is shown in Fig. 8,

illustrating that the free 188ReO4- as well

as the complexes migrated with the sol-

vent front, whereas hydrolyzed rhenium

remained at the origin. By combining the

results of both the TLCs, the complexa-

tion yield was estimated to be >98% in

both cases.

Recovery of Enriched 186Wfrom the Spent Generator

Since enriched 188W is very expensive,

this process could be economically viable

if the adsorbed 186W could be recovered

and reused in many cycles of operation.

Enriched 186W from the exhausted col-

umn was recovered using 5 M NaOH

solution (15 mL NaOH solution +

1 mL 30% H2O2), and the elution

behavior of W from the column is

shown in Fig. 9. It is seen that the

recovery of W is quite fast, and nearly all

the 186W could be eluted out in the first

4–5 mL of the eluent. This step of

desorption of 186W additionally helps in

safe disposal of the column material,

which is an important issue. The recov-

ery of 188Re from W/Re mixture simu-

lated to represent 37 GBq (1 Ci) of188W, was as good when lower amounts

of 188W were used. The overall yields of188Re in the simulated experiments were

*80% and the 188W breakthrough was

<10-3%.

The inherent properties exhibited by

the sorbent (TiP) indicated that it could

be used in the preparation of 188W/188Re

generator.

20 40 60 80 100 1200

20

40

60

80

Per

cent

age

of 18

8 Re

elu

ted

Time (days)

Fig. 4. Performance of the generator

0 20 40 60 80 100 1200.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Rat

io o

f 188W

to 18

8R

e (

Bq/

KB

q)

Elapsed time (days)

Fig. 5. Variation of amount of 188W present in the eluate with time

Original

Discussion

The present study was aimed at explor-

ing the potential advantages of using

polymer embedded nano crystalline

titania (TiP) as an alternative sorbent for

the preparation of 188W/188Re genera-

tors. Our interest in this material sprung

from the recent success in developing a99Mo/99mTc generator [32] using TiP. In

this communication we have focused

only on new progress on the develop-

ment of 188W/188Re generator.

The good physical and chemical sta-

bility of the adsorbent suggests that it

would be well suited for column opera-

tion. This material is also amenable for

column operation with excellent flow

characteristics and attrition resistance.

The time dependence study on sorption

is essential to predict the suspension

times needed for the sorbent to reach

equilibration. It took nearly 45 min for

the sorbent to attain equilibrium.

The high capacity of a sorbent is an

important advantage. The sorbent ap-

pears to have a large amount of

adsorption sites with pronounced

adsorption affinities to retain poly tung-

state species. This feature would be

advantageous in loading large amounts

of 188W on the column while concur-

rently allowing generation of 188Re in

the eluate with high radioactive concen-

tration.

From the perspective of the generator

application, the excellent distribution

ratio (Kd) values for188W over 188Re on

this sorbent in 0.9% NaCl, is particu-

larly heartening and has been exploited

to achieve effective clean separation. In

conjunction with this work that deals

with the sorption of 188W, attempts were

made to correlate the Kd with the zeta

potential. Owing to the positive zeta

potential, the particles can be expected

to enhance the removal of negatively

charged tungstate poly anions from the

aqueous solution at acidic pH. Another

aspect that has emerged clearly from the

present study is that variation of zeta

potential and Kd with pH show a similar

trend. These results give an indication

that the electrostatic force is primarily

responsible for the sorption of 188W in

the present study.

Though the sorption process of

titanium nano composite has been

considered a surface phenomenon, the

possibility of specific chemical interac-

tions between poly tungstate anions

[HW6O21]5- [39] and the sorbent could

also be possible. The selective uptake of

negatively charged poly tungstate ions

may be considered to take place by two

steps. The first one may be due to

electrostatic attraction of negatively

charged anion on the positively charged

surface of the nanocrystalline sorbent

(TiP). Subsequently, it may form a

stable complex of the type [TiW6O24]8-

at this pH range, similar to that re-

ported with alumina [40]. However, in

order to predict the exact mechanism of

188W uptake, further studies are

warranted.

Optimum retention of 188W was

obtained when the pH of the feed was

adjusted in the range of 1–2. The decay of188W to 188Re is not accompanied by any

serious disruption of chemical bonds.188W is expected to be retained strongly

on the sorbent matrix as polymeric

tungstate ions. As these tungstate ions

start transforming into perrhenate ion

(188ReO4-), which has only -1 charge,

the binding would get weaker and an

easy displacement of 188ReO4- is

expected. Therefore, 188Re gets eluted

easily with normal 0.9% saline.

Dynamic absorption capacity ob-

served with this sorbent exhibited

0 1 2 3 4 5 6 7 8 9 100

50000

100000

150000

200000

250000

300000

Act

ivity

(cp

m)

Distance from the point of application (cm)

Fig. 6. Paper chromatographic pattern of the 188ReO4-

0 1 2 3 4 5 6 7 8 9 10

0

5000

10000

15000

20000

25000

Act

ivity

(cp

m)

Distance from the point of application (cm)

188Re-DMSA188Re-HEDP

Fig. 7. Paper chromatographic pattern of 188Re-DMSA and 188Re-HEDP complexes in acetonemedium

Original

marked departure from the static

capacity as a result of the impact of mass

transfer limitations occurred during col-

umn operation. This adsorbent not only

adsorbs more 188W, may be due to the

larger available surface area, but also

binds to it more strongly as a result of

strong electrostatic force, resulting in

low probability of bleed off of the 188W

from the column.

Although, methods such as ICP-AES

[41], direct current argon arc plasma

atomic emission spectroscopy (DCP-

AES) [42], etc. are capable of estimating

low amounts of W in these products,

they are not practical as a routine QC

method. Spectrophotometry [43] could

be a viable method, if a highly specific

complex could be formed with high e. Itis planned to explore this option further

for routine estimation of W.

It was observed that generator con-

taining TiP gives consistently high yields

of 188Re over a prolonged period for

6 months. The elution profile obtained is

sharp and high radioactive concentra-

tion of 188ReO4- could be obtained. The

purity, elution yield of the 188ReO4- and

188W breakthrough remain within per-

missible level with repeated long term

operation. It is important to note that

during the process demonstration run

for a period of 6 months, the flow per-

formance was excellent, no noticeable

fines were observed in the product, and

no column operational problems were

encountered.

The radiochemical as well as radi-

onuclidic purity of 188ReO4- were well

within the acceptable limits. Since the

material used was Ti based, we ascer-

tained that Ti present in the eluted 188Re

was within acceptable limits, using a

sensitive method, such as ICP-AES.

Radiolabeling studies were carried out as

they provide information about the

quality of the separated radiotracers to

form labelled compounds in nano molar

concentrations, which is the final aim in

accessing 188Re.

Another important aspect emerging

from the present study is the recovery of186W + 188W from the spent generator.

When the activity of the 188W decreases

below a certain value, it is no longer

useful for medical application and could

not be discarded without removing the

sorbed 188W. In view of the precious

nature of enriched 186W, all attempts to

recover it and reuse are warranted.

Hence, procedures for removing 186W

along with 188W from the column prior

to disposal were pursed. Washing of the

spent generator with physiological saline

before the W is eluted, facilitates the

depolymerization of tungstate ions

adsorbed on the sorbent surface and

facilitates 186W + 188W desorption.

Recovery of the isotopically enriched186W for further neutron irradiation is

an important part of the economical

production and use of 188W.

Process demonstration run is essen-

tial to evaluate the behavior of the

adsorbent in the presence of intense

radiation environment with the radio-

lytic products generated as a result of

radioactive 188W. It is the physical,

chemical, and radiolytic stability that

determine the suitability of the material

for the preparation of radionuclide gen-

erators. The results of the study for the

separation of 188Re from an 188W/188Re

1 2 3 4 5 6 7 8 9 10

0

10000

20000

30000

40000

50000

60000

70000

80000

Act

ivity

(cp

m)

Distance from the point of application (cm)

188Re-DMSA188Re-HEDP

Fig. 8. Paper chromatographic pattern of 188Re-DMSA and 188Re-HEDP complexes in salinemedium

0 2 4 6 8 10 120

10

20

30

40

50

60

Perc

enta

ge E

lute

d

Volume of NaOH (mL)

Fig. 9. Elution profile of W from the spent column

Original

carrier added solution simulating

37 GBq (1 Ci) generator, provides an

insight into the efficiency of separation

of 188Re from 188W/188Re mixture at

higher levels of activity. However, the

effect of radiation on the performance of

TiP at higher levels of activity is yet to be

demonstrated. Further investigation is

needed to establish the usefulness of TiP

at higher activity levels. However, the

present findings suggest that this mate-

rial TiP holds promise to be a useful

sorbent for the preparation of188W/188Re generator.

Production of 188Re from a generator

containing TiP sorbent possessing high

absorption capacity, could have merits

for utilizing 188W produced from semi-

enriched 186W, in moderate flux research

reactors. This new generator system

based on relatively inexpensive synthe-

sized sorbent material could easily be

adapted by many laboratories. Due to its

operational simplicity, and the possibility

of repeated use of the expensive 186W, this

sorbent is a promising candidate for the

preparation of 188W/188Re generators.

Conclusions

The results of this study demonstrate

that TiP with a significant ion-exchange

capacity is a promising sorbent material

for the preparation of 188W/188Re

radionuclide generator. The material

exhibited high affinity for 188W in com-

parison to 188Re, and hence was suitable

for the separation of 188Re from 188W.

One of the most striking features of this

sorbent was to deliver 188Re with

acceptable radionuclidic, radiochemical

and chemical purity for clinical applica-

tion. Additionally, it was possible to re-

cover the adsorbed 186W + 188W from

the spent generator prior to disposal,

leading to economic advantage. Taking

these into account, we opine that TiP

could be an alternative sorbent in the

preparation of 188W/188Re chromato-

graphic generator using with 186W semi-

enriched target material (50–60%

enrichment) for clinical applications. In

the near future, we envision that

nanomaterials could become critical

components of radionuclide generator

systems.

Acknowledgments

The authors are grateful to Dr. V.

Venugopal, Director, Radiochemistry

and Isotope Group, Bhabha Atomic

Research Centre for his support to this

program. The authors wish to acknowl-

edge Dr. V.K. Manchanda, Head,

Radiochemistry Division and Dr.

S. Ray, Head, Uranium Extraction Divi-

sion of this centre for providing their

facilities for the determination of zeta

potential and ICP analyses respectively.

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Original