Separation of indium-111 from silver cyclotron target material on a 4% cross-linked cation exchanger in nitric acid

ht. J. A&. Radiat. hot. Vol. 36, No. 6, pp. W-503. 198s Q Pergamon Press Ltd 1985. Printed in GreatBritain. W20-708X/85 53.00 + 0.00

of Indium-111 from Silver Cyclotron Target Material on a 4%

Separatioo

Cross-linked

Cation Exchanger

in Nitric

Acid T. N. VAN DER WALT,’ F. W. E. STRELOW’ and R. .I. N. BRITS* ‘National Chemical Research Laboratory, Council for Scientific and Industrial Research and %Jational Accelerator Centre, P. 0. Box 395, Pretoria 0001, Republic of South Africa (Received 23 November 1984) Indium- I1 I can be separated from silver cyclotron target material by eluting silver and copper from a column containing 3.Og of AGSO W-X4 cation exchange resin with 0.30 M nitric acid followed by 0.60 M nitric acid. IndimIll is eluted with 0.50 M hydrochloric acid while trace amounts of iron are retained. Separations are sharp and quantitative. Less than 5 pg of silver were found to remain with the indium-II I when 4g of silver were present originally.

Introduction Indium-I 1I (half-life 67 h) is used in nuclear medicine for tumor imaging,“2’ labeling of lymphocytes,‘*’ neutropl&tr3’ platelets.‘z4’ modifled human fibrinogen,‘J’ monoclonal antibodies and F(ab’h fragments.‘” This radionuclide is usually produced in a cyclotron by a bombardment of a silver taraet throuah the ‘wAg(a.2n) “‘In reaction, or deuteron bomb&dment Gf a cadmium target, the nuclear reactions being ““Cd(d,n) “‘In and “‘Cd(d,2n) “‘In. The action of bremsstrahlung from an electron accelerator “‘Sn(EC,/?‘) “‘In reaction is also through the ‘%b,n) used for production of “‘In.“’ Various separation techniques have been described for the separation of “‘In from the target material, involving co-precipitation and extraction of “‘In,@’ anion exchange chromatography,‘Y.‘u’ solvent extraction of “‘In.“‘~‘~’precipitation of silver as silver chloride and removal by filtration,“3.‘4’ reversed-phase extraction chromatography,(” continuous electrophoresis, t’*’and a combination of solvent extraction and ion exchange chromatography.“‘.‘*’ At the Pretoria cyclotron “‘In is produced by II bombardment of a silver target. The separation method described by Neirinckx(‘9’ was used originally. This involved the coprecipitation of “‘In with-ferric hydroxide by ammonia. Ferric hydroxide was separated by centrifugation of f&ration from the soluble silver in ammoniacal solution. Iron(II1) was then separated from “‘In by solvent extraction from 8.0 M hydrochloric acid into di-isopropyl ether. The extraction was later superseded by a cation exchange separation of “‘In from iron.‘” However, these methods proved to be fairly tedious, rather cumbersome and the final products were contaminated with some ammonium chloride, originating from the co-precipitation step. This salt

was the main component of the fairly high soluble salts content of the “‘In fraction. Consequently, the possibility of using a single column cation exchange separation of “‘In from the silver target material was investigated. According to the distribution coefficients of silver and indium on the cation exchanger AG 5OW-X8’*” one would expect serious tailing of silver when it is eluted with nitric acid of a concentration suitable to give a large separation factor (cc. 0.5-0.6 M). This effect was confirmed by experiments. However, the tailing disappeared when the cation exchanger AG 5OW-X4 was used. This paper presents a simple and rapid cation exchange separation of gram amounts of silver from “‘In using the cation exchanger AG 5OW-X4 and nitric acid as eluting agent.

Experimental Reagents and apparatus Analytical reagent grade chemicals were used. Water was distilled and then deionized. The resin was the AG 5OW-X4 strongly acid sulphonated polystyrene cation exchanger of IO&200 mesh particle size. It was used in the hydrogen form. A borosilicate glass tube (14.6 mm i.d. and 200 mm long) joined to an upper part (20 mm i.d. and 100 mm long) served as a column. The column was fitted with a No. 1 porosity glass sinter and a burette tap at the bottom and a B19 ground sleeve at the top to hold a dropping funnel as a reservoir. The column was filled with a slurry of resin until the settled resin reached a mark at 13.0 mL ( E 3.0 g of dry resin). The resin was washed with 100 mL of 3.0 M nitric acid (to remove traces of chloride impurites) and then equilibrated with 50mL of 0.20 M nitric acid. Atomic absorption measurements were carried out on a Varian-Techtron AA-5 instrument. An automatic Aimer Central Fractionator was used to collect fractions for the preparation of the elution curve. A y-spectrometer. consisting of a Ge(Li) detector, a 4096 channel analyzer and associated electronics, was used to identify and measure the “‘In and lobAg activities. Elution carve A mixture of elements was prepared by dissolving 6.79 g of AgNO,, 0.25 g of CU(NO~)~.~H,O. 6.8 mg In(N0,) ,*5H s0 and 7.2 mg Fe(NO,),.9H,O in 250 mL of 0.20M nitric acid. This solution was passed through an equilibrated resin coltmm. The elements were washed onto the resin with 5 x IO mL of 0.20 M nitric acid. The elements were eluted using the following sequence of reagents: 100 mL of 0.30 M nitric acid and 300 mL of 0.60 M nitric acid to elute silver and copper; 20 mL of 0.01 hydrochloric acid to remove the nitric acid; 160 mL of 0.50 M hydrochloric acid to elute indium and 100 mL of 3.0 M hydrochloric acid to elute iron. A flow-rate of 5.0 + 0.4 mL/min was maintained throughout. Fractions of 20 mL were collected from the beginning of the absorption step. The amounts of the elements in each fraction were determined by atomic absorption spectrometry, using the air-acetylene flame and the 248.3.303.9,324.8 and 328.1 nm lines for iron, indium, copper and silver respectively. The experimental curve is shown in Fig. I. Separation of ‘rrInfrom silver cyclotron target material A cyclotron target was made by melting silver (99.99%) by induction heating in an argon atmosphere onto a copper backing, which could be water cooled. The dimensions of the target were length 135 mm, width 19.5 mm and a silver 501

502

Technical Note O.O?M HCI

CU I

(66mgl Fe (l.OmgI

:

ad

I

200

:

~~xxoxoxi 600

Eluate

(mL)

Fig. I. Elution curve Ag-Cu-In-Fe(II1). 13.0mL (= 3.0g)AG SOW-X4 (H-form, 100-200 mesh). Column length 7.8 mm, 4 14.6 mm. Flow-rate 5.0 k 0.4 mL per minute. thickness of 0.35-0.4Omm. “‘In was produced by bombarding the target with 32 meV a particles for 3.5 h at a beam current of 150 p A. The target was stored for 3 days in order to allow the unwanted short-lived isotopes to decay. The top 0.14 mm silver was then shaved from the target with a milling machine. About 3.8g of silver was obtained containing cu. 1000 MBq “‘In and 33 MBq ‘&Ag. The silver was weighed and dissolved in enough 5.0 M nitric acid to give a final acid concentration of 0.20 M when diluted to 250mL with deionized water. The procedure described above was followed to separate “‘In from the target material, except that 200 mL of 0.60 M nitric acid was used instead of 300mL. The eluates were evaporated when necessary, transferred into IOOmL beakers with the aid of 0.5 M hydrochloric acid and made up to 60 mL volume. “‘In activities were measured in each fraction, the resin column and glassware. ‘*Ag activities were also measured in each fraction. The results are presented in Table 1.

carried out as described above. The ““‘In” fraction was evaporated to about 2 mL volume, quantitatively transferred into a 20 mL volumetric flask and made up to volume with deionized water. Five millilitres of this solution were filtered through a dry Millipore filter (0.22 pm) into a dry 5 mL volumetric flask. Copper and iron were determined in the unfiltered solution and silver was determined in both solutions by atomic absorption spectrometry. The results are presented in Table 2.

Results and Discussion According to the distribution coefficients published by Strelow et ~1.~~‘~ and our experience, serious tailing usually occurs when the distribution coefficients of some elements, including silver, are more than 20 when the cation exchanger AG 5OW-X8 is used. However, with the cation exchanger AG SOW-X4 sharp and quantitative eiutioas can be obtained when operating with distribution coefficients of about 20 or even larger. Using a relatively small resin column “‘In is absorbed as a narrow band at the top of the column. Copper, having a larger distribution coefficient than silver, is absorbed next and any remaining exchange groups will be occupied by silver. When the resin is saturated the excess silver (and copper) will be eluted with 0.30 M nitric acid. Figure I shows that the remaining silver and copper are completely

Determination of silver, copper and iron impurities in the “ “‘In ” fraction Since it was impossible to determine chemical impurities in the radioactive “‘In fraction, a similar experiment was conducted with an inactive target. After cu. 4.1 g of silver had been milled from the top of the target, the silver shavings were dissolved in nitric acid and a separation Table 1. Results of “‘In Fraction Solution before separation

xoarated

“‘“In activity (MB@

33. I ( -+ 5”f) I0

1003 ( +- 5%)

Eluates

(i) absorption step (ii) eluted with 0.20 M HNO, (iii) eluted with 0.60M HNO, (iv) clutcd with 0.6OM HNO, (v) eluted with 0.01 M HCI (vi) eluted with 0.50 M HCI Resin column Glaeswarc

from silver taraet material

“Ob’Ag activity (MW

6.0 250 2.1 2.8 x 10-l
<1x <4x 8x I.1 x c? x 1004 1.0 5.1 x

10-J I)-’ 10-l 10-l 10-z 10-I

Percentage of total (““In activity 100.0
x

<4 x 8x I.1 x <2x loo.1 1.0 x 5.1 x

10-J 10-J 10-J 10-Z 10-J 10-i 10-Z

503

Technical Note Table 2. Imnurities in 8nal ““‘In” fraction Amount of clement bg) Ekn’e’ll Ag (before tiltration)

5.0

CU

0.12

Fe

1.0

Ag (after fikratioa)

1.1

simplifies its recovery when natural or enriched silver targets amused. Acknowfcdgemenrs-The authors wish to thank Dr F. J. Haasbroek for the use of the facilities at the Pretoria Cyclotron Unit of the National Accelerator Centre. References

eluted with 200 mL of 0.60 M nitric acid. Both the absorption of indium and iron are seriously affected by the silver concentration during the absorption step, since the aplicable distribution coefficient of indium decreases with increasing silver concentration. Copper has an even larger influence since it is a divalent cation. Fortunately the amounts of copper are normally fairly small (c 10 mg). After silver and copper have been eluted, the nitric acid is washed from the column with 0.01 M hydrochloric acid. This prevents the iron from moving faster at the interface between 0.60 M nitric acid and 0.50 M hydrochloric acid and its early appearance in the indium fraction. Table 1 shows that an excellent separation of indium is obtained in a typical routine production run. The “‘In produced contained only minute traces of silver, copper and iron (Table 2). The low amount of iron is especially significant because when using the co-precipitation of “‘In with ferric hydroxide”9a’ under routine production conditions, fairly large amounts of iron (up to 20 jrg) were often found in the “‘In fraction. This introduced problems in the preparation of the “‘In oxine complex. No residual ammonium chloride is found in the “‘In fraction with the proposed method. Only y-rays originating from “‘In and lw”Ag were observed. The latter radioisotope is probably produced by the ‘O’Ag(z,zn) ‘*Ag (half-life 8.4 d) reaction. The radioactive contamination of the final product is less than 1 x 10-s Bq per Bq “‘In. When the “‘In fraction is filtered through a Millipore filter (0.22 pm) the amount of silver is reduced considerably (Table 2). After “‘In has been eluted with hydrochloric acid, the eluate can be evaporated to dryness and the “‘In dissolved in the required solvent for further treatment. If the mass of the silver shavings is more than 4.0 g, it is advisable to divide the silver shavings into parts and to use a separate column for each part.

Conclusion The described method presents an excellent means for the production of high purity “‘In, which is superior to products obtained with the previous methods.“9”’ A yield of 95% or better can be obtained under routine separation conditions. The method has proved itself since it has been introduced, and it takes usually less than 3 h to complete the separation, including the target treatment step. It is also important to notice that silver is eluted as the nitrate which

1. Hou D. Y., Hoch H., Johnston G. S., Tsou K. C., Jones A. E.. Farkas R. J. and Miller E. E. J. Surg. Oncol. 25, 168 (1984). 2. Thakur M. L. and GottschaIk A. (Eds). In&m-f11 Labeled Neutrophils, Platelets, and Lymphocytes. Proceedinps of the Yale Svmoosium. September M-15.1979.

(Trivi&m Publishing Company, New York). 3. Thakur M. L., Seifert C. L., Madsen M. T., JMcKenny S. M., Desai A. G. and Park C. H. Semin. Xucl. Med. 14, 107 (1984). 4. Mathias C. J. and Welch M. J. Semin. Nucl. Med. 14, 1 I8 (1984).

5. Lavie E., Bitton M., Ringler G. and Sadeh T. fnt. J. Appl. Radial. Isot. 35, 69 (1984).

6. Powe J., Paik K. Y., Paik C. H., Steplewski Z.. Ebbert M. A., Herlyn D., Ernst C., Alavi A., Eckelman W. C. et al. Chem. Abstr. 101, No. 5282g (1984).

7. Malinin A., Kurenkov N., Koxlova M. and Sevast’yanova A. Radiochem. Radioanal. Lett. 59, 213 (1983).

8. Plotnikov V. I.. Gibova E. G. and Kochetkov V. L. Radiokhimiya 10, 493( 1968). 9. Thakur M. L. and Nunn A. D. ht. J. Appt. Radiarr. Isot. 23, 139 (1972).

10. Vekic B., Horvat V.. Kvastek K. and Hus M. Radiol. lugosl. 16, 171 (1982). II. Gmori T.. Gmori K.. Ochi C.. Yoshihara K. and Yaai M. J. Rahioanal. Nu&. Chem.’ 82, 61 (1984). _ 12. Sharma H. L. and Smith A. G. J. Radioanal. Chem. 64, 249 (1981).

13. Hems F. and Maier-Borst W. Radiochem. Radioanal. Lett. 13, 271 (1973).

14. Shevelev G. A., Troitskaya A. G. and Kartashev V. M. PrikI. Yad. Spektrosk. 6, 295 (1976).

IS. Stronski I. Radiochem. RadionaI. Lett. 5, 113 (1970). 16. Proso Z. and Pucar Z. J. Radioanal. Chem. 3, 187 (1969). 17. Nakamura Y.. Nakahara H. and Murakami Y. Radioisotopes 28, 675 (1979).

18. Kopecky P., Varma K. R. and Mudrova B. Report 1976, WV-3917-C, 21 pp. Avail. INIS. From INIS Atomindex, 8, Abstr. No. 287103 (1977). 19. Neirinckx R. Radiochem. Radioanal. Lett. 4, 153 (1970). 20. Strelow F. W. E. and van der Walt. T. N. 5. Afr. J. Chem. 32, 13(1979). 21. Strelow F. W. E., Rethemeyer R. and Bothma C. J. C. Anal. Chem. 37, 106 (1965).