In cooperation with the Iranian Nuclear Society

Document Type : Research Paper

Authors

Abstract

Nowadays, due to thesuitable decay characteristics and possible production of 68Ga independent of the cyclotron in the form of 68Ge/68Ga generator with reasonable cost, this radionuclide is known as a suitable choice for PET imaging. Recently, SnO2 based 68Ge/68Ga generator was successfully prepared in Iran. In this study, in order to investigate the possible utilization of the made generator in the production and development of 68Ga-based diagnostic radiopharmaceuticals and optimal usage of the generator in the clinical applications, the main characteristics of the generator including the selection of appropriate eluent, elution profile and elution yield were determined, and radionuclidic, chemical and radiochemical purity of the eluate were evaluated. The results of this study indicated that the characteristics of the developed generator in Iran is comparable to those 68Ge/68Ga generators in other countries and it has suitable performance for the usage of developing 68Ga-based PET radiopharmaceuticals.

Highlights

[1] F. Roesch, P.J. Riss, The renaissance of the 68Ge/68Ga radionuclide generator initiates new developments in 68Ga radiopharmaceutical chemistry, Curr Top Med Chem, 10 (2010) 1633-1668.

 

[2] W.A.P. Breeman, A.M. Verbruggen, The 68Ge/68Ga generator has high potential, but when can we use 68Ga-labelled tracers in clinical routine? Eur J Nucl Med Mol Imaging, 34 (2007) 978–981.

 

[3] R. Firestone, Table of isotopes (Shirley VS, editor), 8th edition, John Wiley and Sons Inc, New York (1996).

 

[4] V. Ambrosini, D. Campana, P. Tomassetti, G. Grassetto, D. Rubello, S. Fanti, PET/CT with 68Gallium-DOTA-peptides in NET: An overview, Eur J Radiol, 80 (2011) 116-119.

 

[5] M. Fani, J.P. Andre, H.R. Maecke, 68Ga-PET: A powerful generator-based alternative to cyclotron-based PET radiopharmaceuticals Contrast Media Mol Imaging, 3 (2008) 53-63.

 

[6] M. Pagou, I. Zerizer, A. Al-Nahhas, Can gallium-68 compounds partly replace 18F-FDG in PET molecular imaging? Hellenic J Nucl Med, 12 (2009) 102-105.

 

[7] D.L. Smith, W.A.P. Breeman, J. Sims-Mourtada, The untapped pot ential of Gallium 68-PET: The next wave of 68Ga-agents, Appl Rad Isot, 76 (2013) 14–23.

 

 

[8] M. Hofmann, H. Maecke, R. Borner, E. Weckesser, P. Schoffski, L. Oei, J. Schumacher, M. Henze, A. Heppeler, J.M. eyer, H. Knapp, Biokinetics and imaging
with the somatostatin receptor PET radioligand (68)Ga-DOTATOC: preliminary data, Eur J Nucl Med, 28 (2001) 1751–1757.

 

[9] J. Kowalski, M. Henze, J. Schuhmacher, H.R. Macke, M. Hoffmann, U. Haberkom, Evaluation of positron emission tomography imaging using [68Ga]-DOTA-D-Phe1-Tyr3-octreotide in comparison to [111In]-DTPA-OC SPECT, First results in patients with neuroendocrine tumours, Mol Imaging Biol, 5 (2003) 42–48.

 

[10] F. Rosch, F.F. Knapp, Radionuclide generators, In: A. Vertes, S. Nagy, Z. Klencsar, F. Rosch, editors. Handbook of Nuclear Chemistry, Kluwer Academic Publishers; Dordrecht, The Netherlands, (2003) 81-118.

 

[11] W. Cheng, Y. Jao, C. Lee, A. Lo, Preparation of a 68Ge/68Ga generator with a binary Ga/Ag electrodepositions as solid target, J Radioanal Nucl Chem, 245 (2000) 25-30.

 

[12] K. Aardaneh, T.N. van der Walt, Ga2O for target, solvent extraction for radiochemical separation and SnO2 for the preparation of a 68Ge/68Ga generator, J Radioanal Nucl Chem, 268 (2006) 25-32.

 

[13] B. Bao, M. Song, A new 68Ge/68Ga generator based on CeO2. J Radioanal Nucl Chem, 213 (1996) 233-238.

[14] S.K. Egamediev, S. Khujaev, A.K. Mamatkazina, Influence of the preliminary treatment of aluminium oxide on the 68Ge-68Ga radionuclide chain, J Radioanal Nucl Chem, 246 (2000) 593-596.

 

[15] C. Benhong, L. Zongquan, W. Yongxian, 68Ge-68Ga generator with alpha-ferric oxide support in trigonal structure, J Radioanal Nucl Chem, 238 (1998) 175-177.

 

[16] M. Nakayama, M. Haratake, T. Koiso, O. Ishibashi, K. Harada, H. Nakayama, A. Sugii, S. Yahara, Y. Arano, Separation of 68Ga from 68Ge using a macroporous organic polymer containing N-methylglucamine groups, Anal Chim Acta, 453 (2002) 135–141.

 

[17] M. Nakayama, M. Haratake, M. Ono, T. Koiso, K. Harada, H. Nakayama, S. Yahara, Y. Ohmomo, Y. Arano, A new 68Ge/68Ga generator system using an organic polymer containing N-methylglucamine groups as adsorbent for 68Ge, Appl Radiat Isot, 58 (2003) 9-14.

 

[18] M. Asti, G. De Pietri, A. Fraternali, E. Grassi, R. Sghedoni, F. Fioroni, F. Roesch, A. Versari, D. Salvo, Validation of 68Ge/68Ga generator processing by chemical purification for routine clinical application of 68Ga-DOTATOC, Nucl Med Biol, 35 (2008) 721–724.

 

 

[19] K.P. Zhernosekov, D.V. Filosofov, R.P. Baum, P. Aschoff, H. Bihl, A.A. Razbash, Processing of generator-produced 68Ga for medical application, J Nucl Med, 48 (2007) 1741-1748.

 

[20] E. de Blois, H.S. Chan, C. Naidoo, D. Sedres, E.P. Krenning, W.A.P. Breeman, Characteristics of SnO2-based 68Ge/68Ga generator and aspects of radiolabelling DOTA-peptides, Appl Radiat Isot, 69 (2011) 308-315.

 

[21] C. Decristoforo, R.D. Pickett, A. Verbruggen, Feasibility and availability of 68Ga-labelled peptides, Eur J Nucl Med Mol Imaging, 39 (2012) 31–40.

 

[22] I. Velikyan, G.J. Beyer, B. Långstrom, Microwave-Supported Preparation of 68Ga Bioconjugates with High Specific Radioactivity, Bioconjugate Chem, 15 (2004) 554−560.

 

[23] E. de Blois, H.S. Chan, C. Naidoo, D. Prince, E.P. Krenning, W.A.P. Breeman, Characteristics of SnO2-based 68Ge/68Ga generator and aspects of radiolabelling DOTA-peptides, Appl Rad Isot, 69 (2011) 308–315.

 

[24] European Pharmacopeia: Gallium (68Ga) chloride solution for radiolabelling. European Directorate for the Quality of Medicines, Eur Pharmacopeia, 80(­2464) (2013) 1060–1061.

Keywords

[1] F. Roesch, P.J. Riss, The renaissance of the 68Ge/68Ga radionuclide generator initiates new developments in 68Ga radiopharmaceutical chemistry, Curr Top Med Chem, 10 (2010) 1633-1668.
 
[2] W.A.P. Breeman, A.M. Verbruggen, The 68Ge/68Ga generator has high potential, but when can we use 68Ga-labelled tracers in clinical routine? Eur J Nucl Med Mol Imaging, 34 (2007) 978–981.
 
[3] R. Firestone, Table of isotopes (Shirley VS, editor), 8th edition, John Wiley and Sons Inc, New York (1996).
 
[4] V. Ambrosini, D. Campana, P. Tomassetti, G. Grassetto, D. Rubello, S. Fanti, PET/CT with 68Gallium-DOTA-peptides in NET: An overview, Eur J Radiol, 80 (2011) 116-119.
 
[5] M. Fani, J.P. Andre, H.R. Maecke, 68Ga-PET: A powerful generator-based alternative to cyclotron-based PET radiopharmaceuticals Contrast Media Mol Imaging, 3 (2008) 53-63.
 
[6] M. Pagou, I. Zerizer, A. Al-Nahhas, Can gallium-68 compounds partly replace 18F-FDG in PET molecular imaging? Hellenic J Nucl Med, 12 (2009) 102-105.
 
[7] D.L. Smith, W.A.P. Breeman, J. Sims-Mourtada, The untapped pot ential of Gallium 68-PET: The next wave of 68Ga-agents, Appl Rad Isot, 76 (2013) 14–23.
 
 
[8] M. Hofmann, H. Maecke, R. Borner, E. Weckesser, P. Schoffski, L. Oei, J. Schumacher, M. Henze, A. Heppeler, J.M. eyer, H. Knapp, Biokinetics and imaging
with the somatostatin receptor PET radioligand (68)Ga-DOTATOC: preliminary data, Eur J Nucl Med, 28 (2001) 1751–1757.
 
[9] J. Kowalski, M. Henze, J. Schuhmacher, H.R. Macke, M. Hoffmann, U. Haberkom, Evaluation of positron emission tomography imaging using [68Ga]-DOTA-D-Phe1-Tyr3-octreotide in comparison to [111In]-DTPA-OC SPECT, First results in patients with neuroendocrine tumours, Mol Imaging Biol, 5 (2003) 42–48.
 
[10] F. Rosch, F.F. Knapp, Radionuclide generators, In: A. Vertes, S. Nagy, Z. Klencsar, F. Rosch, editors. Handbook of Nuclear Chemistry, Kluwer Academic Publishers; Dordrecht, The Netherlands, (2003) 81-118.
 
[11] W. Cheng, Y. Jao, C. Lee, A. Lo, Preparation of a 68Ge/68Ga generator with a binary Ga/Ag electrodepositions as solid target, J Radioanal Nucl Chem, 245 (2000) 25-30.
 
[12] K. Aardaneh, T.N. van der Walt, Ga2O for target, solvent extraction for radiochemical separation and SnO2 for the preparation of a 68Ge/68Ga generator, J Radioanal Nucl Chem, 268 (2006) 25-32.
 
[13] B. Bao, M. Song, A new 68Ge/68Ga generator based on CeO2. J Radioanal Nucl Chem, 213 (1996) 233-238.
[14] S.K. Egamediev, S. Khujaev, A.K. Mamatkazina, Influence of the preliminary treatment of aluminium oxide on the 68Ge-68Ga radionuclide chain, J Radioanal Nucl Chem, 246 (2000) 593-596.
 
[15] C. Benhong, L. Zongquan, W. Yongxian, 68Ge-68Ga generator with alpha-ferric oxide support in trigonal structure, J Radioanal Nucl Chem, 238 (1998) 175-177.
 
[16] M. Nakayama, M. Haratake, T. Koiso, O. Ishibashi, K. Harada, H. Nakayama, A. Sugii, S. Yahara, Y. Arano, Separation of 68Ga from 68Ge using a macroporous organic polymer containing N-methylglucamine groups, Anal Chim Acta, 453 (2002) 135–141.
 
[17] M. Nakayama, M. Haratake, M. Ono, T. Koiso, K. Harada, H. Nakayama, S. Yahara, Y. Ohmomo, Y. Arano, A new 68Ge/68Ga generator system using an organic polymer containing N-methylglucamine groups as adsorbent for 68Ge, Appl Radiat Isot, 58 (2003) 9-14.
 
[18] M. Asti, G. De Pietri, A. Fraternali, E. Grassi, R. Sghedoni, F. Fioroni, F. Roesch, A. Versari, D. Salvo, Validation of 68Ge/68Ga generator processing by chemical purification for routine clinical application of 68Ga-DOTATOC, Nucl Med Biol, 35 (2008) 721–724.
 
 
[19] K.P. Zhernosekov, D.V. Filosofov, R.P. Baum, P. Aschoff, H. Bihl, A.A. Razbash, Processing of generator-produced 68Ga for medical application, J Nucl Med, 48 (2007) 1741-1748.
 
[20] E. de Blois, H.S. Chan, C. Naidoo, D. Sedres, E.P. Krenning, W.A.P. Breeman, Characteristics of SnO2-based 68Ge/68Ga generator and aspects of radiolabelling DOTA-peptides, Appl Radiat Isot, 69 (2011) 308-315.
 
[21] C. Decristoforo, R.D. Pickett, A. Verbruggen, Feasibility and availability of 68Ga-labelled peptides, Eur J Nucl Med Mol Imaging, 39 (2012) 31–40.
 
[22] I. Velikyan, G.J. Beyer, B. Långstrom, Microwave-Supported Preparation of 68Ga Bioconjugates with High Specific Radioactivity, Bioconjugate Chem, 15 (2004) 554−560.
 
[23] E. de Blois, H.S. Chan, C. Naidoo, D. Prince, E.P. Krenning, W.A.P. Breeman, Characteristics of SnO2-based 68Ge/68Ga generator and aspects of radiolabelling DOTA-peptides, Appl Rad Isot, 69 (2011) 308–315.
 
[24] European Pharmacopeia: Gallium (68Ga) chloride solution for radiolabelling. European Directorate for the Quality of Medicines, Eur Pharmacopeia, 80(­2464) (2013) 1060–1061.