- Email: [email protected]
Effective separation method of 64Cu from 67Ga waste product with a solvent extraction and chromatography
ARTICLE IN PRESS Applied Radiation and Isotopes 68 (2010) 1623–1626
Contents lists available at ScienceDirect
Applied Radiation and Isotopes journal homepage: www.elsevier.com/locate/apradiso
Effective separation method of 64Cu from extraction and chromatography
67
Ga waste product with a solvent
J.H. Kim a, H. Park b, K.S. Chun b,n a b
Lab. of Accelerator Application Research, Korea Institute of Radiological and Medical Sciences (KIRAMS), 215-4 Gongreung-Dong, Nowon-Gu, Seoul, 139-706 Korea Lab. of Radiopharmaceuticals, Korea Institute of Radiological and Medical Sciences (KIRAMS), 215-4 Gongreung-Dong, Nowon-Gu, Seoul, 139-706 Korea
a r t i c l e in fo
abstract
Article history: Received 19 January 2009 Received in revised form 17 October 2009 Accepted 11 March 2010
A simple chemical process with a solvent extraction was investigated as an effective separation method for 64Cu radionuclide from waste production, which is collected as solution after extracting 67Ga and recovering 68Zn target materials. For the production of radionuclide 67Ga, the enriched 68Zn material electroplated on Cu backing plate is usually exposed to energetic protons. The protons produce 67Ga including other radionuclides, such as 57Ni, 57,55Co, 64,67Cu by several nuclear reactions. After extracting 67 Ga and recovering 68Zn through several steps of chemical processes, the residual solution is usually discarded even though it contains other species of radioisotopes. In this study, a simple chemical process having a high separation efficiency of 64Cu from the waste solution was investigated. With this method, a promising radiotracer as a diagnostic in PET and a therapeutic in radio-immunotherapy, 64Cu was estimated to be produced as high as 1,200 mCi at EOB within 3 h chemical processing after extraction of 67Ga and 68Zn. Crown Copyright & 2010 Published by Elsevier Ltd. All rights reserved.
Keywords: 64 Cu radionuclide Chemical separation Solvent extraction
1. Introduction Copper-64 is one of the most useful and versatile nuclides in nuclear medicine due to its multiple decay schemes, which are the processes of involving on an electron capture (41%), a b decay (40%) and a b + decay (19%), and have an intermediate half-life for radiopharmaceutical synthesis of many compounds (Blower et al., 1996). These properties make its radiopharmaceuticals useful for PET imaging of tumors and targeted radiotherapy labeled on small compounds and monoclonal antibody (Smith, 2004; Cai et al., 2007). Several methods have been investigated for the 64Cu radioisotope production; (i) proton beam irradiation to an enriched 64Ni target material using 64Ni(p,n)64Cu nuclear reaction, (ii) protons with an enriched 68Zn using 68Zn(p,an)64Cu which is side-reaction during the proton beam irradiation on 68Zn target for 67Ga production(Smith et al., 1996), and (iii) deuteron irradiation on an 64Ni using 64Ni(d,2n)64Cu nuclear reactions (Zweit et al., 1991). However, as given in Table 1, each production method has some advantages and disadvantages. From the above mentioned methods, the highest production yields could be obtained with the proton or deuteron beam irradiation on 64 Ni target. However the reliable and effective recovery process for the recycling of enriched 64Ni is absolutely necessary to be established because of the cost of target material. With the costto-product ratio aspect, using the cheaper target material 68Zn is
n
Corresponding author. Tel.: + 82 2 970 1337. E-mail address: [email protected] (K.S. Chun).
more economical for the practical production of 64Cu. Although the production yields of the 68Zn(p,an)64Cu nuclear reaction are lower than those produced from 64Ni target, the former method with chemical extraction process is the most economical processing procedure due to the fact that no extra beam irradiation and no extra recovery process for very expensive enriched material is necessary (Smith et al., 1996). In this paper, we describe an effective separation method of 64 Cu from 67Ga waste solution with dithizone extractant in CCl4 (Dasgupta et al., 1991) and ion chromatography (McCarthy et al., 1997). The 67Ga waste solution used in this work was obtained from the anion exchange column for recovering 68Zn after solvent extraction of 67Ga from 68Zn target, which is a chemical processing procedure established at KIRAMS. A gamma-ray spectrum taken from the waste solution confirmed it contained several radioisotopes such as 57Ni, 57,55Co, 64,67Cu, which were produced by side nuclear reactions during proton irradiation on the 68Zn target as shown in Fig. 1.
2. Materials and methods All reagents used in this work for the production of 64Cu were of analytical grade. The enriched 68Zn (isotopic purity498%) was obtained from Isoflex (Russia). Diisopropyl ether, hydrochloric acid, carbon tetrachloride, dithizone and hydrogen peroxide were purchased from Aldrich. Anion exchange resin AG1-x8 (100 200 mesh) was supplied by BioRad.
0969-8043/$ - see front matter Crown Copyright & 2010 Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.apradiso.2010.03.018
ARTICLE IN PRESS 1624
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Table 1 Possible production routes
64
Cu radioisotope. a
(mCi/mA h)
Production route
Target material
Energy (MeV)
Yield
64
64
64
00
12, 15.5 19 20 26 11.7
1.8, 6.4 10.5 0.2 0.7 0.18
Ni(p,n)64Cu Ni(d,2n)64Cu Nat. Ni(p,n)64Cu 68 Zn(p,an)64Cu 66 Zn(d,a)64Cu a
Ni( 495%) $20,000/g
Natural Ni Zn( 495%) $300/g Zn
68 66
Expected yield per batch(mCi) 720 2,560 (200 mA 2 h) 420 (20 mA 2 h) 400 (200 mA 10 h) 1,400 (200 mA 10 h)
Yields were taken from the article of Smith (2004).
1.0E05
10000
Counts
1000
100
10
1.00
545.00
1088.00 Energy (keV)
Fig. 1. Gamma-ray spectrum was taken from 67Ga waste products after separating Cu. The spectrum was obtained by using HPGe detector coupled with MCA.
67
Ga from
1631.00
2175.00
68
Zn solution. It indicated the production of the radioisotopes of Ni, Co and
67
2.1. Preparation of extractant and anion exchange resin column
2.3. Radionuclide analysis of
The extractant of 64Cu from 67Ga waste product was prepared as a 0.01% dithizone in CCl4. The anion exchange column (j 1 7 cm2) used for purification and concentration of 64Cu solution obtained by dithizone extraction followed by back extraction with 7.2 N HCl was prepared by washing and preequilibrating with deionized water and 7.2 M HCl.
The gamma-ray and radioactivity of radioisotopes contained in the 67Ga product waste were measured with HPGe (High Purity Germanium) detector coupled with MCA (ORTEC EG&G). In order to determine the radioactivity of radioisotopes, the gamma-ray detection efficiencies of HPGe detector were calculated by comparison with a NIST standard source, such as 60Co, 57Co, 133 Ba, 137Cs (Kim et al., 2006) and a few 10 mL of the 67Ga waste was spotted on the filter paper as a small standard source.
2.2. Proton irradiation of
68
Zn target and recovery of
67
Ga waste
Ga waste
The proton beam was irradiated on the 68Zn electroplated on the Cu cooling plate for 67Ga production via the 68Zn(p,2n)67Ga reaction using a 200 mA of 30 MeV proton. After 10 h irradiation, the irradiated 68Zn target was dissolved with 50 ml of 7 M HCl and 67Ga was separated from 68Zn with the solvent extraction system using diisopropyl ether – 7 M HCl. The aqueous phase containing 68Zn and 64Cu including 57Ni, 55Co impurities produced simultaneously by side nuclear reaction during irradiation was saved for 68Zn recovery. For recovery of 68Zn from the aqueous phase, deionized water was added to the aqueous phase to dilute the normality of HCl to 2N and then the solution was loaded on anion exchange column. The eluant from the column containing 64,67 Cu, 57Ni, 55,57Co impurities, which had been discarded as 67Ga product waste, was collected for 64Cu separation. 68Zn retained in column was eluated with deionized water and kept for 68Zn recycling.
2.4. Separation yields of
64
Cu from
67
Ga product waste
The developed 64Cu separation procedure from 67Ga waste is summarized in a flow chart shown in Fig. 2. The 67Ga waste (volume: 350 mL) obtained from the 68Zn recovery anion exchange column, installed in the 67Ga processing hot-cell, was transferred into a 2 L beaker. In order to dilute the normality of HCl of 67Ga waste to 0.5 M, approximately 1 L of deionized water was added to a beaker. For extraction of 64Cu from the 67Ga waste, a 280 mL 0.01% dithizone solution in CCl4 was added to solution and thoroughly mixed for about 5 min. The solution was transferred remotely to separatory funnel with vacuum system and the bottom organic phase containing 64Cu and 67Cu was separated from the aqueous phase. The extracted organic phase was washed with the equal volume of 0.5 N HCl for complete removal of impurities RI from the organic phase. The
ARTICLE IN PRESS J.H. Kim et al. / Applied Radiation and Isotopes 68 (2010) 1623–1626
Fig.2. Flow chart of
67
Ga production and
64
Cu was re-extracted from the organic phase with 30 mL 7.2 N HCl and a few drops of H2O2. The extraction and back-extraction yields of Cu were measured with the intensity of gamma-ray of 64 Cu in each phases obtained with HPGe detector system. The aqueous phase obtained with back extraction was loaded onto anion column (j 1 7 cm2, pre-treated with 7.2 N HCl) at a flowrate of 1 mL/min. In order to recover 64Cu from the column, deionized water was eluted at the same flow rate. The eluted solution was evaporated to dryness under vacuum and then taken up in 1 mL 0.01 M HCl.
3. Results and discussion The identification of radioisotopes which are present in the Ga waste and the quantification of radioactivities were performed by the analysis of peaks of Gamma-rays with HPGe detector system. The gamma-rays of 64Cu, 67Cu, 57Co, 57Ni, 67Ga and 66Ga were confirmed in the 67Ga waste and the radioactivities of each radioisotope are given in Table 2. 64Cu and 67Cu at EOB (End of Bombardment) were estimated as high as 1,208 mCi and 6.05 mCi, respectively. The radioactivity of 67Cu was corrected after Cu separation from the 67Ga waste because the gamma-ray 67
64
Cu separation from
Table 2 Physical properties waste.
b
1625
67
Ga waste.
and radioactivities of radioisotopes found in
67
Ga product
RI
Half-life
Ativity (mCi at EOB)
Gamma-ray (KeV) (abundance, %)
64
12.7 h 61.8 h 78.2 h 35.6 h 17.5 h 271d
1,208 6
511 (34.8), 1345.8 (0.47) 91.3 (7), 93.3 (16), 184.5 (48) 93.3 (39), 184.5 (21), 300.0 (16.6) 127.2 (17), 511 (87), 377.6 (81.7) 477.2 (20), 931.1 (75), 408.5 (17) 122.1 (85.6), 136.5(10.7)
Cu Cu 67 Ga 57 Ni 55 Co 57 Co 67
12 180 o 0.1
b Data were taken from National Nuclear Data Center, Chart of Nuclides, http://www.nndc.bnl.gov.
peaks of 67Cu overlap with 67Ga gamma ray peaks (93 and 184 keV, respectively). The extraction efficiency of 64Cu with 0.01% dithizone in CCl4 was achieved quantitatively higher than 95% and the backextraction to aqueous phase was performed with the one tenth volume of organic phase of 7.2 N HCl. The anion exchange resin was applied for further purification and reducing the volume of 64 Cu solution obtained with the back extraction with 7.2 N HCl.
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1.0E05
10000
Counts
1000
100
10
1.00
545.00
1088.00 Energy (keV)
1631.00
Fig. 3. Gamma-ray spectrum from the final collected solution, which indicated the separation of the
With small size column (j 1 7 cm2), there was no loss of radioactivity during loading and recovering process and finally the volume of solution could be reduced to one fourth. The total processing time and the separation yield of 64Cu from 67 Ga product waste were about 3 h and higher than 90%, respectively. The pure radio-copper 64Cu/67Cu was effectively separated and its radionuclidic purity was checked with HPGeMCA system as shown in Fig. 3. The total extraction efficiency including back extraction and column operation was higher than about 90%. The specific activity of 64Cu is very important factor for radiolabelling application. The specific activity of 64Cu coproduced with 67Ga using the Cu cooling plate electroplated with Ni was measured by Smith group (Smith et al., 1996). In our work, the specific activity of the 64Cu is expected to be low since there is no Ni protecting layer to keep Cu from dissolving off the Cu cooling plated as it is treated with 7 M HCl (Boothe et al., 1991).
4. Conclusion The efficient chemical separation method using solvent extraction (0.01% dithizone in CCl4–HCl) followed by ion exchange chromatography was developed for 64Cu separation from 67 Ga product waste. The procedure developed by our lab was tested with one-fifth volume of 67Ga product waste. The radionuclides in 67Ga waste product obtained from 68Zn recovery system were 64Cu, 67Cu, 67Ga, 57Ni, 55,57Co and the radioactivities of 64Cu and 67Cu were 1200 mCi and 6 mCi at EOB, respectively.
2175.00 64
Cu from the waste solution.
Acknowledgement This work was supported by the Mid- and Long-term Nuclear R&D Program of Ministry of Education and Science Technology (MEST). References Blower, P.J., Lewis, J.S., Zweit, J., 1996. Copper radionuclides and radiopharmaceuticals in nuclear medicine. Nucl. Med. Biol. 23, 957–980. Boothe, T.E., Tavano, E., Munoz, J., Carrol, S., 1991. Coproduction of copper-64 and Copper-67 with Gallium-67 using protons on Zinc-68. J. Labelled Compd. Radiopharm. 30, 108. Cai, W., Chen, K., He, L., Cao, Q., Koong, A., Chen, X., 2007. Quantitative PET of EGFR expression in Xenograft-bearing mice using 64Cu-labeled Cetuximab, a Chimeric anti-EGFR monoclonal antibody. Eur. J. Nucl. Med. Mol. Imaging 34, 850. Dasgupta, A.K., Mausner, L.F., Srivastava, S.C., 1991. A new separation procedure for 67Cu from proton irradiated Zn. Appl. Radiat. Isot. 42 (4), 371–376. Kim, J.H., Park, H., Lee, J.S., Chun, K.S., 2006. Proton beam measurement with a stacked Cu foil techniques for medical radioisotope production. J. Kor. Phy. Soc. 48, 755–758. McCarthy, D.W., Shefer, R.E., Klinkowstein, R.E., Bass, L.A., Margeneau, W.H., Cutler, C.S., Anderson, C.J., Welch, M.J., 1997. Efficient production of high specific activity 64Cu using a biomedical cyclotron. Nucl. Med. Biol. 24, 35–43. Smith, S.V., 2004. Molecular imaging with copper-64. J. Inorg. Biochem. 98, 1874–1901. Smith, S.V., Waters, D.J., Bartolo, N.D., 1996. Separation of 64Cu from 67Ga waste products using anion exchange and low acid aqueous/organic mixtures. Radiochim. Acta 75, 65–68. Zweit, J., Smith, A.M., Downey, S., Sharma, H.L., 1991. Excitation functions for deuteron induced reactions in natural nickel: production of no-carrier-added 64Cu from enriched 64Ni targets for positron emission tomography. Appl. Radiat. Isot. 42 (2), 193–197.
Contents lists available at ScienceDirect
Applied Radiation and Isotopes journal homepage: www.elsevier.com/locate/apradiso
Effective separation method of 64Cu from extraction and chromatography
67
Ga waste product with a solvent
J.H. Kim a, H. Park b, K.S. Chun b,n a b
Lab. of Accelerator Application Research, Korea Institute of Radiological and Medical Sciences (KIRAMS), 215-4 Gongreung-Dong, Nowon-Gu, Seoul, 139-706 Korea Lab. of Radiopharmaceuticals, Korea Institute of Radiological and Medical Sciences (KIRAMS), 215-4 Gongreung-Dong, Nowon-Gu, Seoul, 139-706 Korea
a r t i c l e in fo
abstract
Article history: Received 19 January 2009 Received in revised form 17 October 2009 Accepted 11 March 2010
A simple chemical process with a solvent extraction was investigated as an effective separation method for 64Cu radionuclide from waste production, which is collected as solution after extracting 67Ga and recovering 68Zn target materials. For the production of radionuclide 67Ga, the enriched 68Zn material electroplated on Cu backing plate is usually exposed to energetic protons. The protons produce 67Ga including other radionuclides, such as 57Ni, 57,55Co, 64,67Cu by several nuclear reactions. After extracting 67 Ga and recovering 68Zn through several steps of chemical processes, the residual solution is usually discarded even though it contains other species of radioisotopes. In this study, a simple chemical process having a high separation efficiency of 64Cu from the waste solution was investigated. With this method, a promising radiotracer as a diagnostic in PET and a therapeutic in radio-immunotherapy, 64Cu was estimated to be produced as high as 1,200 mCi at EOB within 3 h chemical processing after extraction of 67Ga and 68Zn. Crown Copyright & 2010 Published by Elsevier Ltd. All rights reserved.
Keywords: 64 Cu radionuclide Chemical separation Solvent extraction
1. Introduction Copper-64 is one of the most useful and versatile nuclides in nuclear medicine due to its multiple decay schemes, which are the processes of involving on an electron capture (41%), a b decay (40%) and a b + decay (19%), and have an intermediate half-life for radiopharmaceutical synthesis of many compounds (Blower et al., 1996). These properties make its radiopharmaceuticals useful for PET imaging of tumors and targeted radiotherapy labeled on small compounds and monoclonal antibody (Smith, 2004; Cai et al., 2007). Several methods have been investigated for the 64Cu radioisotope production; (i) proton beam irradiation to an enriched 64Ni target material using 64Ni(p,n)64Cu nuclear reaction, (ii) protons with an enriched 68Zn using 68Zn(p,an)64Cu which is side-reaction during the proton beam irradiation on 68Zn target for 67Ga production(Smith et al., 1996), and (iii) deuteron irradiation on an 64Ni using 64Ni(d,2n)64Cu nuclear reactions (Zweit et al., 1991). However, as given in Table 1, each production method has some advantages and disadvantages. From the above mentioned methods, the highest production yields could be obtained with the proton or deuteron beam irradiation on 64 Ni target. However the reliable and effective recovery process for the recycling of enriched 64Ni is absolutely necessary to be established because of the cost of target material. With the costto-product ratio aspect, using the cheaper target material 68Zn is
n
Corresponding author. Tel.: + 82 2 970 1337. E-mail address: [email protected] (K.S. Chun).
more economical for the practical production of 64Cu. Although the production yields of the 68Zn(p,an)64Cu nuclear reaction are lower than those produced from 64Ni target, the former method with chemical extraction process is the most economical processing procedure due to the fact that no extra beam irradiation and no extra recovery process for very expensive enriched material is necessary (Smith et al., 1996). In this paper, we describe an effective separation method of 64 Cu from 67Ga waste solution with dithizone extractant in CCl4 (Dasgupta et al., 1991) and ion chromatography (McCarthy et al., 1997). The 67Ga waste solution used in this work was obtained from the anion exchange column for recovering 68Zn after solvent extraction of 67Ga from 68Zn target, which is a chemical processing procedure established at KIRAMS. A gamma-ray spectrum taken from the waste solution confirmed it contained several radioisotopes such as 57Ni, 57,55Co, 64,67Cu, which were produced by side nuclear reactions during proton irradiation on the 68Zn target as shown in Fig. 1.
2. Materials and methods All reagents used in this work for the production of 64Cu were of analytical grade. The enriched 68Zn (isotopic purity498%) was obtained from Isoflex (Russia). Diisopropyl ether, hydrochloric acid, carbon tetrachloride, dithizone and hydrogen peroxide were purchased from Aldrich. Anion exchange resin AG1-x8 (100 200 mesh) was supplied by BioRad.
0969-8043/$ - see front matter Crown Copyright & 2010 Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.apradiso.2010.03.018
ARTICLE IN PRESS 1624
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Table 1 Possible production routes
64
Cu radioisotope. a
(mCi/mA h)
Production route
Target material
Energy (MeV)
Yield
64
64
64
00
12, 15.5 19 20 26 11.7
1.8, 6.4 10.5 0.2 0.7 0.18
Ni(p,n)64Cu Ni(d,2n)64Cu Nat. Ni(p,n)64Cu 68 Zn(p,an)64Cu 66 Zn(d,a)64Cu a
Ni( 495%) $20,000/g
Natural Ni Zn( 495%) $300/g Zn
68 66
Expected yield per batch(mCi) 720 2,560 (200 mA 2 h) 420 (20 mA 2 h) 400 (200 mA 10 h) 1,400 (200 mA 10 h)
Yields were taken from the article of Smith (2004).
1.0E05
10000
Counts
1000
100
10
1.00
545.00
1088.00 Energy (keV)
Fig. 1. Gamma-ray spectrum was taken from 67Ga waste products after separating Cu. The spectrum was obtained by using HPGe detector coupled with MCA.
67
Ga from
1631.00
2175.00
68
Zn solution. It indicated the production of the radioisotopes of Ni, Co and
67
2.1. Preparation of extractant and anion exchange resin column
2.3. Radionuclide analysis of
The extractant of 64Cu from 67Ga waste product was prepared as a 0.01% dithizone in CCl4. The anion exchange column (j 1 7 cm2) used for purification and concentration of 64Cu solution obtained by dithizone extraction followed by back extraction with 7.2 N HCl was prepared by washing and preequilibrating with deionized water and 7.2 M HCl.
The gamma-ray and radioactivity of radioisotopes contained in the 67Ga product waste were measured with HPGe (High Purity Germanium) detector coupled with MCA (ORTEC EG&G). In order to determine the radioactivity of radioisotopes, the gamma-ray detection efficiencies of HPGe detector were calculated by comparison with a NIST standard source, such as 60Co, 57Co, 133 Ba, 137Cs (Kim et al., 2006) and a few 10 mL of the 67Ga waste was spotted on the filter paper as a small standard source.
2.2. Proton irradiation of
68
Zn target and recovery of
67
Ga waste
Ga waste
The proton beam was irradiated on the 68Zn electroplated on the Cu cooling plate for 67Ga production via the 68Zn(p,2n)67Ga reaction using a 200 mA of 30 MeV proton. After 10 h irradiation, the irradiated 68Zn target was dissolved with 50 ml of 7 M HCl and 67Ga was separated from 68Zn with the solvent extraction system using diisopropyl ether – 7 M HCl. The aqueous phase containing 68Zn and 64Cu including 57Ni, 55Co impurities produced simultaneously by side nuclear reaction during irradiation was saved for 68Zn recovery. For recovery of 68Zn from the aqueous phase, deionized water was added to the aqueous phase to dilute the normality of HCl to 2N and then the solution was loaded on anion exchange column. The eluant from the column containing 64,67 Cu, 57Ni, 55,57Co impurities, which had been discarded as 67Ga product waste, was collected for 64Cu separation. 68Zn retained in column was eluated with deionized water and kept for 68Zn recycling.
2.4. Separation yields of
64
Cu from
67
Ga product waste
The developed 64Cu separation procedure from 67Ga waste is summarized in a flow chart shown in Fig. 2. The 67Ga waste (volume: 350 mL) obtained from the 68Zn recovery anion exchange column, installed in the 67Ga processing hot-cell, was transferred into a 2 L beaker. In order to dilute the normality of HCl of 67Ga waste to 0.5 M, approximately 1 L of deionized water was added to a beaker. For extraction of 64Cu from the 67Ga waste, a 280 mL 0.01% dithizone solution in CCl4 was added to solution and thoroughly mixed for about 5 min. The solution was transferred remotely to separatory funnel with vacuum system and the bottom organic phase containing 64Cu and 67Cu was separated from the aqueous phase. The extracted organic phase was washed with the equal volume of 0.5 N HCl for complete removal of impurities RI from the organic phase. The
ARTICLE IN PRESS J.H. Kim et al. / Applied Radiation and Isotopes 68 (2010) 1623–1626
Fig.2. Flow chart of
67
Ga production and
64
Cu was re-extracted from the organic phase with 30 mL 7.2 N HCl and a few drops of H2O2. The extraction and back-extraction yields of Cu were measured with the intensity of gamma-ray of 64 Cu in each phases obtained with HPGe detector system. The aqueous phase obtained with back extraction was loaded onto anion column (j 1 7 cm2, pre-treated with 7.2 N HCl) at a flowrate of 1 mL/min. In order to recover 64Cu from the column, deionized water was eluted at the same flow rate. The eluted solution was evaporated to dryness under vacuum and then taken up in 1 mL 0.01 M HCl.
3. Results and discussion The identification of radioisotopes which are present in the Ga waste and the quantification of radioactivities were performed by the analysis of peaks of Gamma-rays with HPGe detector system. The gamma-rays of 64Cu, 67Cu, 57Co, 57Ni, 67Ga and 66Ga were confirmed in the 67Ga waste and the radioactivities of each radioisotope are given in Table 2. 64Cu and 67Cu at EOB (End of Bombardment) were estimated as high as 1,208 mCi and 6.05 mCi, respectively. The radioactivity of 67Cu was corrected after Cu separation from the 67Ga waste because the gamma-ray 67
64
Cu separation from
Table 2 Physical properties waste.
b
1625
67
Ga waste.
and radioactivities of radioisotopes found in
67
Ga product
RI
Half-life
Ativity (mCi at EOB)
Gamma-ray (KeV) (abundance, %)
64
12.7 h 61.8 h 78.2 h 35.6 h 17.5 h 271d
1,208 6
511 (34.8), 1345.8 (0.47) 91.3 (7), 93.3 (16), 184.5 (48) 93.3 (39), 184.5 (21), 300.0 (16.6) 127.2 (17), 511 (87), 377.6 (81.7) 477.2 (20), 931.1 (75), 408.5 (17) 122.1 (85.6), 136.5(10.7)
Cu Cu 67 Ga 57 Ni 55 Co 57 Co 67
12 180 o 0.1
b Data were taken from National Nuclear Data Center, Chart of Nuclides, http://www.nndc.bnl.gov.
peaks of 67Cu overlap with 67Ga gamma ray peaks (93 and 184 keV, respectively). The extraction efficiency of 64Cu with 0.01% dithizone in CCl4 was achieved quantitatively higher than 95% and the backextraction to aqueous phase was performed with the one tenth volume of organic phase of 7.2 N HCl. The anion exchange resin was applied for further purification and reducing the volume of 64 Cu solution obtained with the back extraction with 7.2 N HCl.
ARTICLE IN PRESS 1626
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1.0E05
10000
Counts
1000
100
10
1.00
545.00
1088.00 Energy (keV)
1631.00
Fig. 3. Gamma-ray spectrum from the final collected solution, which indicated the separation of the
With small size column (j 1 7 cm2), there was no loss of radioactivity during loading and recovering process and finally the volume of solution could be reduced to one fourth. The total processing time and the separation yield of 64Cu from 67 Ga product waste were about 3 h and higher than 90%, respectively. The pure radio-copper 64Cu/67Cu was effectively separated and its radionuclidic purity was checked with HPGeMCA system as shown in Fig. 3. The total extraction efficiency including back extraction and column operation was higher than about 90%. The specific activity of 64Cu is very important factor for radiolabelling application. The specific activity of 64Cu coproduced with 67Ga using the Cu cooling plate electroplated with Ni was measured by Smith group (Smith et al., 1996). In our work, the specific activity of the 64Cu is expected to be low since there is no Ni protecting layer to keep Cu from dissolving off the Cu cooling plated as it is treated with 7 M HCl (Boothe et al., 1991).
4. Conclusion The efficient chemical separation method using solvent extraction (0.01% dithizone in CCl4–HCl) followed by ion exchange chromatography was developed for 64Cu separation from 67 Ga product waste. The procedure developed by our lab was tested with one-fifth volume of 67Ga product waste. The radionuclides in 67Ga waste product obtained from 68Zn recovery system were 64Cu, 67Cu, 67Ga, 57Ni, 55,57Co and the radioactivities of 64Cu and 67Cu were 1200 mCi and 6 mCi at EOB, respectively.
2175.00 64
Cu from the waste solution.
Acknowledgement This work was supported by the Mid- and Long-term Nuclear R&D Program of Ministry of Education and Science Technology (MEST). References Blower, P.J., Lewis, J.S., Zweit, J., 1996. Copper radionuclides and radiopharmaceuticals in nuclear medicine. Nucl. Med. Biol. 23, 957–980. Boothe, T.E., Tavano, E., Munoz, J., Carrol, S., 1991. Coproduction of copper-64 and Copper-67 with Gallium-67 using protons on Zinc-68. J. Labelled Compd. Radiopharm. 30, 108. Cai, W., Chen, K., He, L., Cao, Q., Koong, A., Chen, X., 2007. Quantitative PET of EGFR expression in Xenograft-bearing mice using 64Cu-labeled Cetuximab, a Chimeric anti-EGFR monoclonal antibody. Eur. J. Nucl. Med. Mol. Imaging 34, 850. Dasgupta, A.K., Mausner, L.F., Srivastava, S.C., 1991. A new separation procedure for 67Cu from proton irradiated Zn. Appl. Radiat. Isot. 42 (4), 371–376. Kim, J.H., Park, H., Lee, J.S., Chun, K.S., 2006. Proton beam measurement with a stacked Cu foil techniques for medical radioisotope production. J. Kor. Phy. Soc. 48, 755–758. McCarthy, D.W., Shefer, R.E., Klinkowstein, R.E., Bass, L.A., Margeneau, W.H., Cutler, C.S., Anderson, C.J., Welch, M.J., 1997. Efficient production of high specific activity 64Cu using a biomedical cyclotron. Nucl. Med. Biol. 24, 35–43. Smith, S.V., 2004. Molecular imaging with copper-64. J. Inorg. Biochem. 98, 1874–1901. Smith, S.V., Waters, D.J., Bartolo, N.D., 1996. Separation of 64Cu from 67Ga waste products using anion exchange and low acid aqueous/organic mixtures. Radiochim. Acta 75, 65–68. Zweit, J., Smith, A.M., Downey, S., Sharma, H.L., 1991. Excitation functions for deuteron induced reactions in natural nickel: production of no-carrier-added 64Cu from enriched 64Ni targets for positron emission tomography. Appl. Radiat. Isot. 42 (2), 193–197.