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Carrier-free separation of 111In from a silver matrix
Pergamon
0969-8043(95)00264-2
Appl. Radiat. Isot. Vol. 47, No. 3, pp. 293-296, 1996 Copyright © 1996 Elsevier Science Ltd Printed in Great Britain. All rights reserved 0969-8043/96 $15.00 + 0.00
Carrier-free Separation of Silver Matrix S. K. D A S , R. G U I N
from a
a n d S. K. S A H A *
Radiochemistry Laboratory, Variable Energy Cyclotron Centre, Bhabha Atomic Research Centre, I/AF Bidhan nagar, Calcutta 700 064, India (Received 15 June 1995)
A radiochemical procedure for the separation of carrier-free m ln from an Ag matrix is described. ~HIn is produced by the bombardment of a natural Ag target by ~t-particles. The method involves the removal of bulk silver by chloride precipitation followed by anion exchange separation of the HtIn from the trace amount of Ag still present after chloride precipitation.
Introduction The cyclotron produced isotope, ~ti In by virtue of its suitable half-life (2.8 days), absence of fl-emission and low-energy y-emissions of 171 keV (89%) and 245 keV (94%) is well suited for diagnostic nuclear medicine. Among many diagnostic nuclear medicine procedures the most important involve the use of Ill In-labelled blood cells, rain-labelled monoclonal antibodies, m In-DTPA and IH In-leukocytes. One of the main uses of HI In is in the non-invasive diagnosis (Thakur, 1982) of malignant lesions. Furthermore, radiolabelled blood cells permit quantitative monitoring of in vivo cell distribution and migration patterns. Hlln also has potential (Harbert, 1984; Price, 1984) for radioimmunoscintigraphy, cisternography and lymphoscintigraphy. rain emits the 171 and 245 keV ~-rays in a cascade in which the intermediate nuclear level has a suitable lifetime (84nsc) for use as a nuclear probe for perturbed angular correlation (PAC) studies, m In is one of the most popular nuclear probes for PAC. Applications of the PAC technique using HI In in different fields of research, viz. solid state physics, chemistry and biology have been reviewed elsewhere (Rinneberg, 1979; Das, 1991). In these applications it is desirable to have the m In in carrier-free form. Ill In is produced in cyclotrons mainly through the Cd(p,xn) (Brown and Beets, 1972) and Ag(~,xn) (Thakur and Nunn, 1972; Neirinckx, 1970) reactions. With cadmium as the target, the enriched isotope tl2Cd has to be used in order to avoid the production of the long-lived isotope, l14In (TI/2 --- 49 days) which is produced when natural Cd is used as the target. *To whom all correspondence should be addressed.
When silver is used as target material this problem is avoided because the ~t-induced reaction on Ag produces mainly HI In. Other activities produced by this reaction are short-lived and, therefore, can be allowed to decay out. It is well known that the radionuclide, when used for medical purposes, has to be both chemically and radiochemically pure. Stringent conditions are imposed for the purity of the substance. Similarly, PAC studies require carrier-free activity which should not contain any other activity or chemical impurities but H~In which simply acts as a probe for the matrix to be studied. Separation methods of indium from different matrices described elsewhere (Sunderman and Townley, 1960) are not suitable for the uses mentioned above. A chemical separation method (Neirinckx, 1970) for Ill In from an Ag matrix in volves the coprecipitation of In with Fe and removal of the Fe by solvent extraction. However, the extent of Fe-decontamination is not quantitative. In this work we present a chemical separation which avoids the coprecipitation step and gives a quantitative estimate of the contamination of Ag in the final m In fraction. Experimental Irradiation
Natural Ag metal foil of thickness 26.6 mg/cm 2 (supplied by LEIKO Industries Inc., NY) has been used as the target. The excitation functions for (~t,xn) reaction on l°Ta°gAg are known (Guin et al., 1992). The ~t-beam energy of 30 meV was chosen to maximize the production of thin via the (~t,2n) reaction on ~°gAg. The beam current was restricted
293
S.K. Das et al.
294
to ~<1 g A and the target was water cooled to avoid target deterioration due to heating during irradiation.
Chemical separation After irradiation the target was stored for 24 h to allow the 1°°In (Tla = 4.9 h) to decay to an insignificant level. The Ag metal target was then dissolved in concentrated HNO3; lt°mAg was added to this solution as tracer to estimate the contamination of Ag in the final l ' I n activity. This solution was evaporated to dryness and dissolved in a minimum amount of water, an excess of 6 M HC1 was added to precipitate the Ag as AgCi. The solution was then centrifuged to separate out Ag from the solution; a few drops of HCI were then added to check the completeness of the precipitation reaction. About 98% of the Ag initially present was removed by the precipitation step and the loss of In was found to be less than 5%. After separation of the major quantity of Ag by this method, the clear solution containing the In activity was evaporated almost to dryness and the solution was brought to 11 M with respect to HCI. A measured volume (3 mL) of this solution was loaded on to a Dowex 2 x 8 (200-400 mesh) column of dimensions 5 cm long and 5 mm dia previously conditioned with 11 M hydrochloric acid. Loading and washing were carried out with 11 M HCI. The flow rate was maintained at 4-5 drops/min. 1 mL HCI aliquots of the elute were used to monitor the elution pattern of both Ag and In; elution was continued until the y-lines belonging to H°mAg became almost insignificant. Finally, the In was eluted quantitatively in cartier-free form with 2 ml of water. The same experiment was repeated using 9 and 3 M HC1 to determine the best conditions for the separation of In from Ag.
Gamma spectrometry To monitor the degree of purity of the ~ll In activity separated from the Ag target and to measure the chemical yield of rain, the activities at each stage of separation were measured using a high-purity Ge detector, having 15% efficiency, coupled to a 4 K multichannel analyser. The detector resolution was found to be 1.8 keV for the 1332 keV 6°Co photopeak. Liquid samples of constant volume were positioned in a fixed geometry at a distance of about 15cm from the detector. The y-lines at 658 keV for the ll0mAg tracer and 171 and 245 keV for m ln were monitored for each sample. The spectra were recorded on a floppy disk for subsequent analyses.
cartier-free i11In from a bulk amount of Ag. It has been observed that In(III) adsorbs quite strongly on Dowex 2 x 8 anion exchange column in HCI. The adsorption increases as the acidity increases. At 11 M HCI, only about 10% of the In could be eluted with 4 mL eluent while Ag was removed quantitatively due to the formation of anionic complexes (Kraus et ai., 1954), viz. InClf 3 or InClf which are stable at higher HCI concentrations. In dilute acid or in neutral medium different cationic species e.g. InCl,', InOH ÷2, In +3, may exist and therefore In is easily eluted from the anion exchange column with 3 M HC1. Water was found to be an even better eluent for the elution of In. Indium could be eluted quantitatively with 2 mL of water. Therefore, after the removal of Ag, water was chosen as the eluent for In in carrier-free form. Table 1 describes the ion exchange behaviour at 3, 9 and 11 M HCI. In 3 M HCI, even though In could be quantitatively eluted, some Ag contamination was always observed in the In fraction. In 9 M HCI, Ag is eluted much more slowly, thus, by the time Ag is completely removed, the loss of In is significant. Therefore, 11 M HC1 was chosen for the decontamination of Ag from In. The chemical yield of rollIn (clean fraction of In only) was 85%. The y-spectra for the H°mAg+ lltIn activity mixture before loading on to the anion exchanger and that of the pure Ill In fraction are shown in Figs la and b, respectively. Figure lb clearly indicates that the m In activity is almost free from any Ag contamination. However, to determine the level of Ag contamination, the pure In fraction was counted for a long time (about 20h) and the decontamination factor for Ag was estimated to be 106. The solid content present in the pure In fraction was estimated by evaporating the solution under an i.r. lamp. The solid residue was found to be negligible. Therefore, the In activity had been recovered in carrier-free form. Because of the large reaction cross-section the yield of rain in a typical irradiation is quite high (5 MBq//~Ah). The time taken for the whole chemical separation is about 1 h and considering the chemical yield and purity of the lllln activity the present method of separation of lllIn is suitable for the routine preparation of carrier-free ill In from an Ag matrix for medical purposes or as a probe for PAC. Furthermore, since the final solution of rain is aqueous, it can be used for these purposes, without further evaporation steps.
Table 1. Elution behaviour of In and Ag in different concentrations of HCI
Results and Discussion The separation of In from Ag was carried out at different acid concentrations to determine the ion-exchange behaviour of In and Ag in an acid medium and to select the best conditions for the separation of
Eluent 11 M HCI 9 M HCI 3 M HCI
Volume of eluent (mL) 4 5 6
Amount eluted (%) Ag
In
100 95 2.2
9.7 10.0 100
Carrier-free separation of m In
295
30,000
25,000 0
7 20,000
>
i
-
I I
15,000
o
10,000
500o
~,
.~>°
<
I
C)
25,000
20,000
15,000
I 0,000
5000
0
I
!
500
i 000
1500
Channel No. Fig. I. Gamma spectra for m In and ll°~Ag: (a) before separation; and (b) after separation.
Acknowledgements--The authors wish to thank Dr D. D. Sood, Director, Radiochemistry and Isotope Group, BARC, Dr R. H. Iyer, Head, Radiochemistry Division, BARC and Dr B. C. Sinha, Director, VECC for their keen interest in this work. Thanks are also due to the cyclotron crew members, VECC for their co-operation during the irradiations.
References
Brown L. C. and Beets A. L. (1972) Cyclotron production of carrier-free indium-I 11. Int. J. Appl. Radiat. Isot. 23, 57. Das S. K. (1991) Chemical studies using gamma-gamma perturbed angular correlation. Ph.D. Thesis,
Guin R., Saha S. K., Satya P. and Uhl M. (1992) Isomeric yield ratios and excitation functions in ,c-induced reactions on t°zl°gAg. Phys. Rev. C 48, 250. Harbert J. (1984) Radionuclid¢ cisternography. In Textbook of Nuclear Medicine, Vol. II: Clinical Applications (Edited by Harbert John and Fernando Goncalves Da Rocha), p. Ill. Kraus K. A., Nelson F. and Smith G. W. (1954) Anionexchange Studies. IX. Adsorbability of a number of metal in hydrochloric acid solutions. J. Phys. Chem. 58, 11. Neirinckx R. D. (1970) The separation of cyclotron-produced ttt ln from a silver matrix. Radiochem. Radioanal. Lett. 4) 153. Price D. C. (1984) The lymphatic system. In Textbook of Nuclear Medicine, Vol. H: Clinical Applications (Edited by
296
S.K. Das et al.
Harbert John and Fernando Goncalves Da Rocha), p. 609. Rinneberg H. H. (1979) Application of perturbed angular correlation to chemistry and related areas of solid state physics. Atom. Energy Rev. 17, 477. Sunderman D. N. and Townley C. W. (1960) Radiochemistry of indium. NAS-NS-3014.
Thakur M. L. (1982) Radiolabeled blood cells: agents for diagnostic and kinetic studies. In Applications o f Nuclear and Radiochemistry (Edited by Lambrecht Richard M. and Morcos Nabil), Chap. 11, p. 115. Pergamon Press, Oxford. Thakur M. L. and Nunn A. D. (1972) Cyclotron produced indium-! 11 for medical use. Int. J. Appl. Radiat. Isot. 23, 139.
0969-8043(95)00264-2
Appl. Radiat. Isot. Vol. 47, No. 3, pp. 293-296, 1996 Copyright © 1996 Elsevier Science Ltd Printed in Great Britain. All rights reserved 0969-8043/96 $15.00 + 0.00
Carrier-free Separation of Silver Matrix S. K. D A S , R. G U I N
from a
a n d S. K. S A H A *
Radiochemistry Laboratory, Variable Energy Cyclotron Centre, Bhabha Atomic Research Centre, I/AF Bidhan nagar, Calcutta 700 064, India (Received 15 June 1995)
A radiochemical procedure for the separation of carrier-free m ln from an Ag matrix is described. ~HIn is produced by the bombardment of a natural Ag target by ~t-particles. The method involves the removal of bulk silver by chloride precipitation followed by anion exchange separation of the HtIn from the trace amount of Ag still present after chloride precipitation.
Introduction The cyclotron produced isotope, ~ti In by virtue of its suitable half-life (2.8 days), absence of fl-emission and low-energy y-emissions of 171 keV (89%) and 245 keV (94%) is well suited for diagnostic nuclear medicine. Among many diagnostic nuclear medicine procedures the most important involve the use of Ill In-labelled blood cells, rain-labelled monoclonal antibodies, m In-DTPA and IH In-leukocytes. One of the main uses of HI In is in the non-invasive diagnosis (Thakur, 1982) of malignant lesions. Furthermore, radiolabelled blood cells permit quantitative monitoring of in vivo cell distribution and migration patterns. Hlln also has potential (Harbert, 1984; Price, 1984) for radioimmunoscintigraphy, cisternography and lymphoscintigraphy. rain emits the 171 and 245 keV ~-rays in a cascade in which the intermediate nuclear level has a suitable lifetime (84nsc) for use as a nuclear probe for perturbed angular correlation (PAC) studies, m In is one of the most popular nuclear probes for PAC. Applications of the PAC technique using HI In in different fields of research, viz. solid state physics, chemistry and biology have been reviewed elsewhere (Rinneberg, 1979; Das, 1991). In these applications it is desirable to have the m In in carrier-free form. Ill In is produced in cyclotrons mainly through the Cd(p,xn) (Brown and Beets, 1972) and Ag(~,xn) (Thakur and Nunn, 1972; Neirinckx, 1970) reactions. With cadmium as the target, the enriched isotope tl2Cd has to be used in order to avoid the production of the long-lived isotope, l14In (TI/2 --- 49 days) which is produced when natural Cd is used as the target. *To whom all correspondence should be addressed.
When silver is used as target material this problem is avoided because the ~t-induced reaction on Ag produces mainly HI In. Other activities produced by this reaction are short-lived and, therefore, can be allowed to decay out. It is well known that the radionuclide, when used for medical purposes, has to be both chemically and radiochemically pure. Stringent conditions are imposed for the purity of the substance. Similarly, PAC studies require carrier-free activity which should not contain any other activity or chemical impurities but H~In which simply acts as a probe for the matrix to be studied. Separation methods of indium from different matrices described elsewhere (Sunderman and Townley, 1960) are not suitable for the uses mentioned above. A chemical separation method (Neirinckx, 1970) for Ill In from an Ag matrix in volves the coprecipitation of In with Fe and removal of the Fe by solvent extraction. However, the extent of Fe-decontamination is not quantitative. In this work we present a chemical separation which avoids the coprecipitation step and gives a quantitative estimate of the contamination of Ag in the final m In fraction. Experimental Irradiation
Natural Ag metal foil of thickness 26.6 mg/cm 2 (supplied by LEIKO Industries Inc., NY) has been used as the target. The excitation functions for (~t,xn) reaction on l°Ta°gAg are known (Guin et al., 1992). The ~t-beam energy of 30 meV was chosen to maximize the production of thin via the (~t,2n) reaction on ~°gAg. The beam current was restricted
293
S.K. Das et al.
294
to ~<1 g A and the target was water cooled to avoid target deterioration due to heating during irradiation.
Chemical separation After irradiation the target was stored for 24 h to allow the 1°°In (Tla = 4.9 h) to decay to an insignificant level. The Ag metal target was then dissolved in concentrated HNO3; lt°mAg was added to this solution as tracer to estimate the contamination of Ag in the final l ' I n activity. This solution was evaporated to dryness and dissolved in a minimum amount of water, an excess of 6 M HC1 was added to precipitate the Ag as AgCi. The solution was then centrifuged to separate out Ag from the solution; a few drops of HCI were then added to check the completeness of the precipitation reaction. About 98% of the Ag initially present was removed by the precipitation step and the loss of In was found to be less than 5%. After separation of the major quantity of Ag by this method, the clear solution containing the In activity was evaporated almost to dryness and the solution was brought to 11 M with respect to HCI. A measured volume (3 mL) of this solution was loaded on to a Dowex 2 x 8 (200-400 mesh) column of dimensions 5 cm long and 5 mm dia previously conditioned with 11 M hydrochloric acid. Loading and washing were carried out with 11 M HCI. The flow rate was maintained at 4-5 drops/min. 1 mL HCI aliquots of the elute were used to monitor the elution pattern of both Ag and In; elution was continued until the y-lines belonging to H°mAg became almost insignificant. Finally, the In was eluted quantitatively in cartier-free form with 2 ml of water. The same experiment was repeated using 9 and 3 M HC1 to determine the best conditions for the separation of In from Ag.
Gamma spectrometry To monitor the degree of purity of the ~ll In activity separated from the Ag target and to measure the chemical yield of rain, the activities at each stage of separation were measured using a high-purity Ge detector, having 15% efficiency, coupled to a 4 K multichannel analyser. The detector resolution was found to be 1.8 keV for the 1332 keV 6°Co photopeak. Liquid samples of constant volume were positioned in a fixed geometry at a distance of about 15cm from the detector. The y-lines at 658 keV for the ll0mAg tracer and 171 and 245 keV for m ln were monitored for each sample. The spectra were recorded on a floppy disk for subsequent analyses.
cartier-free i11In from a bulk amount of Ag. It has been observed that In(III) adsorbs quite strongly on Dowex 2 x 8 anion exchange column in HCI. The adsorption increases as the acidity increases. At 11 M HCI, only about 10% of the In could be eluted with 4 mL eluent while Ag was removed quantitatively due to the formation of anionic complexes (Kraus et ai., 1954), viz. InClf 3 or InClf which are stable at higher HCI concentrations. In dilute acid or in neutral medium different cationic species e.g. InCl,', InOH ÷2, In +3, may exist and therefore In is easily eluted from the anion exchange column with 3 M HC1. Water was found to be an even better eluent for the elution of In. Indium could be eluted quantitatively with 2 mL of water. Therefore, after the removal of Ag, water was chosen as the eluent for In in carrier-free form. Table 1 describes the ion exchange behaviour at 3, 9 and 11 M HCI. In 3 M HCI, even though In could be quantitatively eluted, some Ag contamination was always observed in the In fraction. In 9 M HCI, Ag is eluted much more slowly, thus, by the time Ag is completely removed, the loss of In is significant. Therefore, 11 M HC1 was chosen for the decontamination of Ag from In. The chemical yield of rollIn (clean fraction of In only) was 85%. The y-spectra for the H°mAg+ lltIn activity mixture before loading on to the anion exchanger and that of the pure Ill In fraction are shown in Figs la and b, respectively. Figure lb clearly indicates that the m In activity is almost free from any Ag contamination. However, to determine the level of Ag contamination, the pure In fraction was counted for a long time (about 20h) and the decontamination factor for Ag was estimated to be 106. The solid content present in the pure In fraction was estimated by evaporating the solution under an i.r. lamp. The solid residue was found to be negligible. Therefore, the In activity had been recovered in carrier-free form. Because of the large reaction cross-section the yield of rain in a typical irradiation is quite high (5 MBq//~Ah). The time taken for the whole chemical separation is about 1 h and considering the chemical yield and purity of the lllln activity the present method of separation of lllIn is suitable for the routine preparation of carrier-free ill In from an Ag matrix for medical purposes or as a probe for PAC. Furthermore, since the final solution of rain is aqueous, it can be used for these purposes, without further evaporation steps.
Table 1. Elution behaviour of In and Ag in different concentrations of HCI
Results and Discussion The separation of In from Ag was carried out at different acid concentrations to determine the ion-exchange behaviour of In and Ag in an acid medium and to select the best conditions for the separation of
Eluent 11 M HCI 9 M HCI 3 M HCI
Volume of eluent (mL) 4 5 6
Amount eluted (%) Ag
In
100 95 2.2
9.7 10.0 100
Carrier-free separation of m In
295
30,000
25,000 0
7 20,000
>
i
-
I I
15,000
o
10,000
500o
~,
.~>°
<
I
C)
25,000
20,000
15,000
I 0,000
5000
0
I
!
500
i 000
1500
Channel No. Fig. I. Gamma spectra for m In and ll°~Ag: (a) before separation; and (b) after separation.
Acknowledgements--The authors wish to thank Dr D. D. Sood, Director, Radiochemistry and Isotope Group, BARC, Dr R. H. Iyer, Head, Radiochemistry Division, BARC and Dr B. C. Sinha, Director, VECC for their keen interest in this work. Thanks are also due to the cyclotron crew members, VECC for their co-operation during the irradiations.
References
Brown L. C. and Beets A. L. (1972) Cyclotron production of carrier-free indium-I 11. Int. J. Appl. Radiat. Isot. 23, 57. Das S. K. (1991) Chemical studies using gamma-gamma perturbed angular correlation. Ph.D. Thesis,
Guin R., Saha S. K., Satya P. and Uhl M. (1992) Isomeric yield ratios and excitation functions in ,c-induced reactions on t°zl°gAg. Phys. Rev. C 48, 250. Harbert J. (1984) Radionuclid¢ cisternography. In Textbook of Nuclear Medicine, Vol. II: Clinical Applications (Edited by Harbert John and Fernando Goncalves Da Rocha), p. Ill. Kraus K. A., Nelson F. and Smith G. W. (1954) Anionexchange Studies. IX. Adsorbability of a number of metal in hydrochloric acid solutions. J. Phys. Chem. 58, 11. Neirinckx R. D. (1970) The separation of cyclotron-produced ttt ln from a silver matrix. Radiochem. Radioanal. Lett. 4) 153. Price D. C. (1984) The lymphatic system. In Textbook of Nuclear Medicine, Vol. H: Clinical Applications (Edited by
296
S.K. Das et al.
Harbert John and Fernando Goncalves Da Rocha), p. 609. Rinneberg H. H. (1979) Application of perturbed angular correlation to chemistry and related areas of solid state physics. Atom. Energy Rev. 17, 477. Sunderman D. N. and Townley C. W. (1960) Radiochemistry of indium. NAS-NS-3014.
Thakur M. L. (1982) Radiolabeled blood cells: agents for diagnostic and kinetic studies. In Applications o f Nuclear and Radiochemistry (Edited by Lambrecht Richard M. and Morcos Nabil), Chap. 11, p. 115. Pergamon Press, Oxford. Thakur M. L. and Nunn A. D. (1972) Cyclotron produced indium-! 11 for medical use. Int. J. Appl. Radiat. Isot. 23, 139.