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Separation of 111Ag from neutron irradiated natural palladium using alumina as an adsorbent
Applied Radiation and Isotopes 52 (2000) 19±22
www.elsevier.com/locate/apradiso
Separation of 111Ag from neutron irradiated natural palladium using alumina as an adsorbent M. Khalid a, A. Mushtaq a,*, M.Z. Iqbal b a
Radioisotope Production Group, Nuclear Chemistry Division, Pakistan Institute of Nuclear Science and Technology, P.O. Nilore, Islamabad, Pakistan. b Institute of Chemistry, Punjab University, Lahore Pakistan. Received 28 January 1999; received in revised form 7 April 1999; accepted 23 April 1999
Abstract A simple method is presented for the separation of no-carrier-added 111Ag from neutron irradiated natural palladium. The method is based on sorption of 111Ag in 0.01 M HCl on alumina. Palladium is removed by washing with 0.1 M HCl and the 111Ag is eluted with 4 M HCl. The overall yields of 111Ag are better than 85% with <1 mg/ ml palladium as an impurity. The whole procedure from dissolving the target to the ®nal 111Ag solution takes about 2 h. # 2000 Elsevier Science Ltd. All rights reserved.
1. Introduction In order to develop eective radiopharmaceuticals for therapy, it is essential to consider carefully the choices of appropriate radionuclides in conjunction with the in vivo localization and pharmokinetics properties of the radiotracer (Wessles and Rogus, 1984; Schlom, 1986; Spencer et al., 1987). The use of antibodies labelled with appropriate radionuclides to deliver therapeutic doses of radiation for human cancer treatment has now been shown to give clinically signi®cant eects in a number of studies (Stewart et al., 1990; Paganelli et al., 1995). 111Ag has been suggested to be more suitable for radioimmunotherapy than the commonly used 131I on the basis of its good bÿ emission characteristics, (Eb max 1.05 MeV) appropriate half life (7.5 d) and much more favourable g-ray component (342 keV, 6% for 111Ag compared with 364
* Corresponding author. Fax: +92-51-929-0275. E-mail address: [email protected] (A. Mushtaq).
keV, 82% for 131I) (Browne and Firestone, 1986; Schubiger, 1989). 111 Ag is produced as follows: 110
bÿ
Pd n, g111m,111 Pd ÿ ÿ4 ÿ
22 m, 5:5 h
111m
1T
Agÿ ÿ4 ÿ 111 Ag 1:2 m
Thus, the neutron irradiation of Pd in a reactor provides a source of no-carrier-added 111Ag and, if the target material is cooled for a day or more, only 103Pd, 109 Pd and 111Ag are expected to be present. Various methods have been reported in the literature for the separation of 111Ag from irradiated palladium. The method reported by Haymond et al. (1950) for the separation of radioactive silver from the spallation products of Pd is rather elaborate and lengthy. Schweitzer and Nehls (1952) utilized the radiocolloidal properties of silver in tracer concentration, however the recovery of Ag in the radiocolloid form was not satisfactory and always contaminated with Pd (Lyle and Maghzian, 1968). The low stability of complexes formed by Ag relative to that of Pd with chelate type ion exchange resin has also been mentioned for the
0969-8043/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved. PII: S 0 9 6 9 - 8 0 4 3 ( 9 9 ) 0 0 0 8 3 - 4
20
M. Khalid et al. / Applied Radiation and Isotopes 52 (2000) 19±22
separation of Ag (Lyle and Maghzian, 1968). Taylor (1961) and Mirza (1970) reported the separation of Ag from Pd based on the rapid elution of 111Ag with 10 M HCl from anion exchange resin column. A cation exchanger has been also utilized for the sorption of complex amine cations of Ag and Pd, selective elution of 111Ag was carried out with 0.5 M NaCl (Mansur et al., 1995). In another method 111Ag is extracted quantitatively together with small amount of Pd, from an aqueous solution into toluene by complexation with triphenylphosphine and subsequently 111Ag is reextracted selectively into a buer solution (Alberto et al., 1992). In this work, 111Ag was sorbed on alumina in 0.01 M HCl solution. Pd was washed o with 0.1 M HCl while 4 M HCl was employed for the desorption of 111 Ag.
2. Experimental Palladium metal wire (The British Drug Houses) was used as a target material. Al2O3 (90 active acidic l for column chromatography 70±230 mesh ASTM) was purchased from E. Merck Germany and other reagents were of analytical grade. The radioactivity was measured by g-ray spectrometry using a coaxial Gedetector coupled to a Canberra series 85 multichannel analyzer. 2.1. Irradiation Known quantities of natural palladium targets were sealed in quartz ampoules and cold welded in to aluminum cans. The irradiations were carried out inside the core of the 9 MW swimming pool type Pakistan Atomic Research Reactor I (PARR-I) for up to 72 h at a neutron ¯ux of 01014 cmÿ2 sÿ1. 2.1.1. Pd/111Ag solution The irradiated targets were cooled for 35 h and dissolved in aqua regia (5 ml). The solution was heated to dryness with repeated addition of concentrated HCl to expel the last traces of HNO3. Finally the residue was dissolved in 0.01 M HCl. 2.1.2. Sorption of 109Pd/111Ag on alumina A total of 5 ml of the aqueous solution of the desired molarity containing 1 mg Pd/5 ml and no-carrier-added 111Ag was shaken at room temperature with 100 mg alumina for 1 h. The supernatant was separated after centrifugation and counted for 111Ag (245 keV (1.1%), 342 keV (6%) and 109Pd (88 keV, 3.7%)) against the standard. The distribution coecient was calculated by the formula
Fig. 1. Sorption of mesh).
Kd
111
Ag and
109
Pd on alumina (70±230
Amount of 109 Pd or 111 Ag=g Al2 O3 Amount of 109 Pd or 111 Ag=ml of liquid phase
2.1.3. Separation of 109Pd and 111Ag on alumina The alumina was treated 4 times with 5 M HCl and redistilled water and the ®ne particles were discarded. A glass ®lter column (1 cm diameter 10 cm high) was ®lled with 5 g alumina and washed with 0.01 M HCl solution. The solution containing 100 mg irradiated palladium and the 111Ag in 30 ml of 0.01 M HCl was passed through the alumina column at a rate of 01 ml/min. The column was washed with 60 ml of 0.1 M HCl to remove the Pd completely and 111Ag was eluted with 30±40 ml of 4 M HCl solution. 2.2. Spot test for palladium A ®lter paper was dipped into a saturated solution of dimethylglyoxime in ethanol. The ®lter paper was dried and dipped into slightly ammoniacal 5% nickel nitrate solution. The paper was brie¯y washed with
M. Khalid et al. / Applied Radiation and Isotopes 52 (2000) 19±22
Fig. 2. Separation of
111
Ag and
21
109
Pd on alumina (70±230 mesh) (5 g). Column: 1 10 cm, ¯ow rate: 1 ml/min.
distilled water, dipped into ethanol and dried. On this ®lter paper (dimethylglyoximate test paper), one drop of slightly acidic test solution was placed. After drying, it was immersed in dilute HCl and washed with H2O. A red colour remaining only where the test solution was applied indicated Pd. Standards of 10, 5, 4, 3, 2 and 1 mg /ml Pd were prepared (IUPAC, 1964) and compared for the presence of Pd in the separated 111 Ag.
3. Results and discussion The results of the adsorption of 109Pd and 111Ag from 0.01 to 10 M HCl solution are shown in Fig.1 (Kd versus acid concentration). It is evident that the sorption of Pd from 0.1 to 10 M HCl is not signi®cant while in the case of 111Ag the Kd values increase sharply from 1 to 0.01 M HCl. The curves for 111Ag and 109 Pd are nearly the same, however the dierences in the distribution coecient (Kd) values are large enough for the separation of these two elements at 0.01 and 0.1 M HCl concentration on alumina. The separation of 109Pd and 111Ag on an alumina column is shown in Fig.2. It shows that the Pd is quantitatively removed with 0.01 and 0.1 M HCl solution. 0.1 M HCl solution was used to accelerate the removal of Pd from the column. Small amounts (3±6%) of 111Ag were also detected in these washings. More than 80% of 111Ag can be eluted with 20 ml of 4 M HCl solution. The
whole procedure from dissolving the target to the ®nal 111 Ag solution takes about 2 h. The concentration of Pd in 111Ag eluate was determined by measuring the 88 keV g-rays of 109mAg, the daughter product of 109Pd. Since no 88 keV g-rays of 109m Ag was found in 111Ag eluate, a spot test for Pd was carried out with nickel dimethylglyoximate paper and compared with standards. No positive test of Pd was observed, thus, it was assumed that the concentration of Pd in 111Ag eluate was less than 1 mg Pd/ml. The alumina is superior to organic resins in their thermal and radiation stability and its use as an adsorbent will also exclude the possibility of contaminating the ®nal product with organic matter, which may interfere with some labelling procedures.
References Alberto, R., Blauenstein, P., Novak-Hofer, I., Smith, A., Schubiger, P.A., 1992. An improved method for the separation of 111Ag from irradiated natural palladium. Appl. Radiat. Isot. 43, 868. Browne, E., Firestone, R.B., 1986. In: Shirley, V.S. (Ed.), Table of Radioactive Isotopes. John Wiley and Sons, New York. Haymond, H.R., Carson, K.H., Maxwell, R.D., Garrison, W.M., Hamilton, 1950. Carrier-free radioisotopes from cyclotrom targets VI. Preparation and isolation of Ag 105,106,111 from palladium. J. Chem. Phys. 18, 319. IUPAC, 1964. Reagents and Reactions for Qualitative Inorganic Analysis. 5th Report. Butterworths, London.
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M. Khalid et al. / Applied Radiation and Isotopes 52 (2000) 19±22
Lyle, S.J., Maghzian, R., 1968. Separation of carrier free Ag111 from irradiated palladium. Talanta 15, 712. Mansur, M.S., Mushtaq, A., Ali, Muhammad, 1995. Separation of 111Ag from neutron irradiated natural palladium. Radiochim. Acta 68, 161. Mirza, M.Y., 1970. Separation of carrier free 111Ag from neutron irradiated palladium. Radiochim. Acta 14, 61. Paganelli, G., Magnani, P., Siccardi, A.G., Fazio, F., 1995. In: Goldenberg, D.M. (Ed.), Cancer Therapy with Radiolabelled Antibodies. CRC press, Boca Raton, USA, p. 239. Schlom, J., 1986. Basic principles and applications of monoclonal antibodies in the management of carcinomas. Cancer Res. 46, 3225. Schubiger, P.A., 1989. Neue Radionuklide in der Diagnostik und Therapie Trends zur Reduzierung Strahlenbelastung. In: Koehnlein, W., Trout, H., Fischer, M. (Eds.), Die Wirkung niedriger Strahlendosen. Springer verlag, Berlin.
Schweitzer, G.K., Nehls, J.W., 1952. Studies in low concentration chemistry II. The radiocolloid properties of silver111. J. Am. Chem. Soc. 74, 6186. Spencer, R.P., Suvers, R.H., Friedman, A.M., 1987. Radionuclides in Therapy. CRC Press, Boca Raton. Stewart, J.S.W., Hird, V., Snook, D., Dhokia, B., Sivolapenko, G., Hooker, G., Taylor-Papadimitriou, J., Rowlinson, G., Sullivan, M., Lambert, H.E., Coulter, C., Mason, W.P., Souter, W.P., Epenetos, A.A., 1990. Intraperitoneal yttrium-90 labelled monoclonal antibody in ovarian cancer. J. Clin. Oncol. 8 (12), 1941. Taylor, D.M., 1961. The preparation of carrier-free silver-111. Int. J. Appl. Radiat. Isot. 12, 66. Wessles, B.W., Rogus, R.D., 1984. Radionclide selection and model absorbed dose calculations for radiolabelled tumor associated antibodies. Med. Phys. 11, 638.
www.elsevier.com/locate/apradiso
Separation of 111Ag from neutron irradiated natural palladium using alumina as an adsorbent M. Khalid a, A. Mushtaq a,*, M.Z. Iqbal b a
Radioisotope Production Group, Nuclear Chemistry Division, Pakistan Institute of Nuclear Science and Technology, P.O. Nilore, Islamabad, Pakistan. b Institute of Chemistry, Punjab University, Lahore Pakistan. Received 28 January 1999; received in revised form 7 April 1999; accepted 23 April 1999
Abstract A simple method is presented for the separation of no-carrier-added 111Ag from neutron irradiated natural palladium. The method is based on sorption of 111Ag in 0.01 M HCl on alumina. Palladium is removed by washing with 0.1 M HCl and the 111Ag is eluted with 4 M HCl. The overall yields of 111Ag are better than 85% with <1 mg/ ml palladium as an impurity. The whole procedure from dissolving the target to the ®nal 111Ag solution takes about 2 h. # 2000 Elsevier Science Ltd. All rights reserved.
1. Introduction In order to develop eective radiopharmaceuticals for therapy, it is essential to consider carefully the choices of appropriate radionuclides in conjunction with the in vivo localization and pharmokinetics properties of the radiotracer (Wessles and Rogus, 1984; Schlom, 1986; Spencer et al., 1987). The use of antibodies labelled with appropriate radionuclides to deliver therapeutic doses of radiation for human cancer treatment has now been shown to give clinically signi®cant eects in a number of studies (Stewart et al., 1990; Paganelli et al., 1995). 111Ag has been suggested to be more suitable for radioimmunotherapy than the commonly used 131I on the basis of its good bÿ emission characteristics, (Eb max 1.05 MeV) appropriate half life (7.5 d) and much more favourable g-ray component (342 keV, 6% for 111Ag compared with 364
* Corresponding author. Fax: +92-51-929-0275. E-mail address: [email protected] (A. Mushtaq).
keV, 82% for 131I) (Browne and Firestone, 1986; Schubiger, 1989). 111 Ag is produced as follows: 110
bÿ
Pd n, g111m,111 Pd ÿ ÿ4 ÿ
22 m, 5:5 h
111m
1T
Agÿ ÿ4 ÿ 111 Ag 1:2 m
Thus, the neutron irradiation of Pd in a reactor provides a source of no-carrier-added 111Ag and, if the target material is cooled for a day or more, only 103Pd, 109 Pd and 111Ag are expected to be present. Various methods have been reported in the literature for the separation of 111Ag from irradiated palladium. The method reported by Haymond et al. (1950) for the separation of radioactive silver from the spallation products of Pd is rather elaborate and lengthy. Schweitzer and Nehls (1952) utilized the radiocolloidal properties of silver in tracer concentration, however the recovery of Ag in the radiocolloid form was not satisfactory and always contaminated with Pd (Lyle and Maghzian, 1968). The low stability of complexes formed by Ag relative to that of Pd with chelate type ion exchange resin has also been mentioned for the
0969-8043/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved. PII: S 0 9 6 9 - 8 0 4 3 ( 9 9 ) 0 0 0 8 3 - 4
20
M. Khalid et al. / Applied Radiation and Isotopes 52 (2000) 19±22
separation of Ag (Lyle and Maghzian, 1968). Taylor (1961) and Mirza (1970) reported the separation of Ag from Pd based on the rapid elution of 111Ag with 10 M HCl from anion exchange resin column. A cation exchanger has been also utilized for the sorption of complex amine cations of Ag and Pd, selective elution of 111Ag was carried out with 0.5 M NaCl (Mansur et al., 1995). In another method 111Ag is extracted quantitatively together with small amount of Pd, from an aqueous solution into toluene by complexation with triphenylphosphine and subsequently 111Ag is reextracted selectively into a buer solution (Alberto et al., 1992). In this work, 111Ag was sorbed on alumina in 0.01 M HCl solution. Pd was washed o with 0.1 M HCl while 4 M HCl was employed for the desorption of 111 Ag.
2. Experimental Palladium metal wire (The British Drug Houses) was used as a target material. Al2O3 (90 active acidic l for column chromatography 70±230 mesh ASTM) was purchased from E. Merck Germany and other reagents were of analytical grade. The radioactivity was measured by g-ray spectrometry using a coaxial Gedetector coupled to a Canberra series 85 multichannel analyzer. 2.1. Irradiation Known quantities of natural palladium targets were sealed in quartz ampoules and cold welded in to aluminum cans. The irradiations were carried out inside the core of the 9 MW swimming pool type Pakistan Atomic Research Reactor I (PARR-I) for up to 72 h at a neutron ¯ux of 01014 cmÿ2 sÿ1. 2.1.1. Pd/111Ag solution The irradiated targets were cooled for 35 h and dissolved in aqua regia (5 ml). The solution was heated to dryness with repeated addition of concentrated HCl to expel the last traces of HNO3. Finally the residue was dissolved in 0.01 M HCl. 2.1.2. Sorption of 109Pd/111Ag on alumina A total of 5 ml of the aqueous solution of the desired molarity containing 1 mg Pd/5 ml and no-carrier-added 111Ag was shaken at room temperature with 100 mg alumina for 1 h. The supernatant was separated after centrifugation and counted for 111Ag (245 keV (1.1%), 342 keV (6%) and 109Pd (88 keV, 3.7%)) against the standard. The distribution coecient was calculated by the formula
Fig. 1. Sorption of mesh).
Kd
111
Ag and
109
Pd on alumina (70±230
Amount of 109 Pd or 111 Ag=g Al2 O3 Amount of 109 Pd or 111 Ag=ml of liquid phase
2.1.3. Separation of 109Pd and 111Ag on alumina The alumina was treated 4 times with 5 M HCl and redistilled water and the ®ne particles were discarded. A glass ®lter column (1 cm diameter 10 cm high) was ®lled with 5 g alumina and washed with 0.01 M HCl solution. The solution containing 100 mg irradiated palladium and the 111Ag in 30 ml of 0.01 M HCl was passed through the alumina column at a rate of 01 ml/min. The column was washed with 60 ml of 0.1 M HCl to remove the Pd completely and 111Ag was eluted with 30±40 ml of 4 M HCl solution. 2.2. Spot test for palladium A ®lter paper was dipped into a saturated solution of dimethylglyoxime in ethanol. The ®lter paper was dried and dipped into slightly ammoniacal 5% nickel nitrate solution. The paper was brie¯y washed with
M. Khalid et al. / Applied Radiation and Isotopes 52 (2000) 19±22
Fig. 2. Separation of
111
Ag and
21
109
Pd on alumina (70±230 mesh) (5 g). Column: 1 10 cm, ¯ow rate: 1 ml/min.
distilled water, dipped into ethanol and dried. On this ®lter paper (dimethylglyoximate test paper), one drop of slightly acidic test solution was placed. After drying, it was immersed in dilute HCl and washed with H2O. A red colour remaining only where the test solution was applied indicated Pd. Standards of 10, 5, 4, 3, 2 and 1 mg /ml Pd were prepared (IUPAC, 1964) and compared for the presence of Pd in the separated 111 Ag.
3. Results and discussion The results of the adsorption of 109Pd and 111Ag from 0.01 to 10 M HCl solution are shown in Fig.1 (Kd versus acid concentration). It is evident that the sorption of Pd from 0.1 to 10 M HCl is not signi®cant while in the case of 111Ag the Kd values increase sharply from 1 to 0.01 M HCl. The curves for 111Ag and 109 Pd are nearly the same, however the dierences in the distribution coecient (Kd) values are large enough for the separation of these two elements at 0.01 and 0.1 M HCl concentration on alumina. The separation of 109Pd and 111Ag on an alumina column is shown in Fig.2. It shows that the Pd is quantitatively removed with 0.01 and 0.1 M HCl solution. 0.1 M HCl solution was used to accelerate the removal of Pd from the column. Small amounts (3±6%) of 111Ag were also detected in these washings. More than 80% of 111Ag can be eluted with 20 ml of 4 M HCl solution. The
whole procedure from dissolving the target to the ®nal 111 Ag solution takes about 2 h. The concentration of Pd in 111Ag eluate was determined by measuring the 88 keV g-rays of 109mAg, the daughter product of 109Pd. Since no 88 keV g-rays of 109m Ag was found in 111Ag eluate, a spot test for Pd was carried out with nickel dimethylglyoximate paper and compared with standards. No positive test of Pd was observed, thus, it was assumed that the concentration of Pd in 111Ag eluate was less than 1 mg Pd/ml. The alumina is superior to organic resins in their thermal and radiation stability and its use as an adsorbent will also exclude the possibility of contaminating the ®nal product with organic matter, which may interfere with some labelling procedures.
References Alberto, R., Blauenstein, P., Novak-Hofer, I., Smith, A., Schubiger, P.A., 1992. An improved method for the separation of 111Ag from irradiated natural palladium. Appl. Radiat. Isot. 43, 868. Browne, E., Firestone, R.B., 1986. In: Shirley, V.S. (Ed.), Table of Radioactive Isotopes. John Wiley and Sons, New York. Haymond, H.R., Carson, K.H., Maxwell, R.D., Garrison, W.M., Hamilton, 1950. Carrier-free radioisotopes from cyclotrom targets VI. Preparation and isolation of Ag 105,106,111 from palladium. J. Chem. Phys. 18, 319. IUPAC, 1964. Reagents and Reactions for Qualitative Inorganic Analysis. 5th Report. Butterworths, London.
22
M. Khalid et al. / Applied Radiation and Isotopes 52 (2000) 19±22
Lyle, S.J., Maghzian, R., 1968. Separation of carrier free Ag111 from irradiated palladium. Talanta 15, 712. Mansur, M.S., Mushtaq, A., Ali, Muhammad, 1995. Separation of 111Ag from neutron irradiated natural palladium. Radiochim. Acta 68, 161. Mirza, M.Y., 1970. Separation of carrier free 111Ag from neutron irradiated palladium. Radiochim. Acta 14, 61. Paganelli, G., Magnani, P., Siccardi, A.G., Fazio, F., 1995. In: Goldenberg, D.M. (Ed.), Cancer Therapy with Radiolabelled Antibodies. CRC press, Boca Raton, USA, p. 239. Schlom, J., 1986. Basic principles and applications of monoclonal antibodies in the management of carcinomas. Cancer Res. 46, 3225. Schubiger, P.A., 1989. Neue Radionuklide in der Diagnostik und Therapie Trends zur Reduzierung Strahlenbelastung. In: Koehnlein, W., Trout, H., Fischer, M. (Eds.), Die Wirkung niedriger Strahlendosen. Springer verlag, Berlin.
Schweitzer, G.K., Nehls, J.W., 1952. Studies in low concentration chemistry II. The radiocolloid properties of silver111. J. Am. Chem. Soc. 74, 6186. Spencer, R.P., Suvers, R.H., Friedman, A.M., 1987. Radionuclides in Therapy. CRC Press, Boca Raton. Stewart, J.S.W., Hird, V., Snook, D., Dhokia, B., Sivolapenko, G., Hooker, G., Taylor-Papadimitriou, J., Rowlinson, G., Sullivan, M., Lambert, H.E., Coulter, C., Mason, W.P., Souter, W.P., Epenetos, A.A., 1990. Intraperitoneal yttrium-90 labelled monoclonal antibody in ovarian cancer. J. Clin. Oncol. 8 (12), 1941. Taylor, D.M., 1961. The preparation of carrier-free silver-111. Int. J. Appl. Radiat. Isot. 12, 66. Wessles, B.W., Rogus, R.D., 1984. Radionclide selection and model absorbed dose calculations for radiolabelled tumor associated antibodies. Med. Phys. 11, 638.