Journal of Nuclear Science, Engineering and Technology (JONSAT)
In cooperation with the Iranian Nuclear Society

Characterization of the second generation of Pars-GalluGen generator (68Ge/68Ga generator) and quality control of its eluate

Document Type : Scientific Note

Authors

M. Gholamhosseini-Nazari
A. Rahiminezhad
M. Gilani
M. Hahsemizadeh
H. Masoumi
R. Sardari
H. Naderi

Pars Isotope Company, P.O.Box: 17376-63181, Tehran – Iran

https://doi.org/10.24200/nst.2024.1648
Abstract
Gallium-68 (68Ga) is a radionuclide widely used for diagnostic purposes in Nuclear Medicine. With the availability of 68Ge/68Ga generators, the radiopharmaceutical industry is currently focused on developing this generator. The development and application of 68Ge/68Ga generators remain a hot topic in nuclear medicine. In recent years, Pars Isotope Company in Iran has produced 68Ge/68Ga generators (Pars-GalluGen generator) that are eluted with 5 ml of 0.6 M hydrochloric acid. Additionally, Pars Isotope has developed the second generation of Pars-GalluGen generators. This new generator is based on a SnO2-TiO2 resin matrix and is eluted with 3 ml 0.1 M hydrochloric acid. This research aimed to determine the main characteristics of the second generation of Pars-GalluGen generators and evaluate their quality control. The results obtained indicate that this generator meets all specifications of the European Pharmacopoeia for use and has better performance characteristics, including higher chemical, radiochemical, and radionuclide purity, as well as a higher elution yield compared to the first generation.

Highlights

  1. Nelson B.J, Andersson J.D, Wuest F, Spreckelmeyer S. Good practices for 68Ga radiopharmaceutical production. EJNMMI Radiopharmacy and Chemistry. 2022 Dec;7(1):1-26.

 

  1. Rösch F. Past, present and future of 68Ge/68Ga generators. Applied Radiation and Isotopes. 2013 Jun 1;76:24-30.

 

  1. Jalilian A.R. An overview on Ga-68 radiopharmaceuticals for positron emission tomography applications. Iranian Journal of Nuclear Medicine. 2016;24(1):1.

 

  1. Roesch F. Maturation of a key resource–the germanium-68/gallium-68 generator: development and new insights. Current Radiopharmaceuticals. 2012 Jul 1;5(3):202-11.

 

  1. Meisenheimer M, Saenko Y, Eppard E. Gallium-68: Radiolabeling of Radiopharmaceuticals for PET Imaging—A Lot to Consider. Med Isot. 2019 Dec 23.

 

  1. Tsionou M.I, Knapp C.E, Foley C.A, Munteanu C.R, Cakebread A, Imberti C, Eykyn T.R, Young J.D, Paterson B.M, Blower P.J, Ma M.T. Comparison of macrocyclic and acyclic chelators for gallium-68 radiolabelling. RSC advances. 2017;7(78):49586-99.

 

  1. Lenzo N.P, Meyrick D, Turner J.H. Review of gallium-68 PSMA PET/CT imaging in the management of prostate cancer. Diagnostics. 2018 Feb 11;8(1):16.

 

  1. Rodnick M.E, Sollert C, Stark D, Clark M, Katsifis A, Hockley B.G, Parr D.C, Frigell J, Henderson B.D, Bruton L, Preshlock S. Synthesis of 68Ga-radiopharmaceuticals using both generator-derived and cyclotron-produced 68Ga as exemplified by [68Ga] Ga-PSMA-11 for prostate cancer PET imaging. Nature Protocols. 2022 Apr;17(4):980-1003.

 

  1. Okarvi S.M. Recent developments of prostate-specific membrane antigen (PSMA)-specific radiopharmaceuticals for precise imaging and therapy of prostate cancer: an overview. Clinical and Translational Imaging. 2019 Jun 1;7:189-208.

 

  1. Rodnick M.E, Sollert C, Stark D, Clark M, Katsifis A, Hockley B.G, Parr D.C, Frigell J, Henderson B.D, Abghari-Gerst M, Piert M.R. Cyclotron-based production of 68Ga, [68Ga] GaCl3, and [68Ga] Ga-PSMA-11 from a liquid target. EJNMMI Radiopharmacy and Chemistry. 2020 Dec;5:1-8.

 

  1. Hamed M.A, Basha M.A, Ahmed H, Obaya A.A, Afifi A.H, Abdelbary E.H. 68Ga-PSMA PET/CT in patients with rising prostatic-specific antigen after definitive treatment of prostate cancer: detection efficacy and diagnostic accuracy. Academic Radiology. 2019 Apr 1;26(4):450-60.

 

  1. Weitzer F, Pernthaler B, Plhak E, Riedl R, Aigner R.M. Diagnostic value of two-time point [68Ga] Ga-PSMA-11 PET/CT in the primary staging of untreated prostate cancer. Scientific Reports. 2023 May 22;13(1):8297.

 

  1. Maffey-Steffan J, Scarpa L, Svirydenka A, Nilica B, Mair C, Buxbaum S, Bektic J, Von Guggenberg E, Uprimny C, Horninger W, Virgolini I. The 68Ga/177Lu-theragnostic concept in PSMA-targeting of metastatic castration–resistant prostate cancer: impact of post-therapeutic whole-body scintigraphy in the follow-up. European journal of nuclear medicine and molecular imaging. 2020 Mar;47:695-712.

 

  1. Peters S.M, Hofferber R, Privé B.M, De Bakker M, Gotthardt M, Janssen M, De Lange F, Muselaers C.H, Mehra N, Witjes J.A, Costa P.F. [68Ga] Ga-PSMA-11 PET imaging as a predictor for absorbed doses in organs at risk and small lesions in [177Lu] Lu-PSMA-617 treatment. European Journal of Nuclear Medicine and Molecular Imaging. 2022 Mar 1:1-2.

 

  1. Zha Z, Choi S.R, Li L, Zhao R, Ploessl K, Yao X, Alexoff D, Zhu L, Kung H.F. New PSMA-Targeting Ligands: Transformation from Diagnosis (Ga-68) to Radionuclide Therapy (Lu-177). Journal of Medicinal Chemistry. 2022 Sep 14;65(19):13001-12.

 

  1. Sinnes J.P, Bauder-Wüst U, Schäfer M, Moon E.S, Kopka K, Rösch F. 68Ga, 44Sc and 177Lu-labeled AAZTA 5-PSMA-617: synthesis, radiolabeling, stability and cell binding compared to DOTA-PSMA-617 analogues. EJNMMI radiopharmacy and chemistry. 2020 Dec;5:1-1.

 

  1. Stenvall A, Gustafsson J, Larsson E, Roth D, Sundlöv A, Jönsson L, Hindorf C, Ohlsson T, Sjögreen Gleisner K. Relationships between uptake of [68Ga] Ga-DOTA-TATE and absorbed dose in [177Lu] Lu-DOTA-TATE therapy. EJNMMI research. 2022 Dec;12(1):1-5.

 

  1. Sainz-Esteban A, Prasad V, Schuchardt C, Zachert C, Carril J.M, Baum R.P. Comparison of sequential planar 177Lu-DOTA-TATE dosimetry scans with 68Ga-DOTA-TATE PET/CT images in patients with metastasized neuroendocrine tumours undergoing peptide receptor radionuclide therapy. European journal of nuclear medicine and molecular imaging. 2012 Mar;39:501-11.

 

  1. Hennrich U, Benešová M. [68Ga] Ga-DOTA-TOC: the first FDA-approved 68Ga-radiopharmaceutical for PET imaging. Pharmaceuticals. 2020 Mar 3;13(3):38.

 

  1. Breeman W.A, De Jong M, De Blois E, Bernard B.F, Konijnenberg M, Krenning E.P. Radiolabelling DOTA-peptides with 68Ga. European journal of nuclear medicine and molecular imaging. 2005 Apr;32:478-85.

 

  1. Kilian K. 68Ga-DOTA and analogs: Current status and future perspectives. Reports of Practical Oncology & Radiotherapy. 2014 May 1;19:S13-21.

 

  1. Fani M, Mansi R, Nicolas G.P, Wild D. Radiolabeled somatostatin analogs—a continuously evolving class of radiopharmaceuticals. Cancers. 2022 Feb 24;14(5):1172.

 

  1. Martiniova L, Palatis L.D, Etchebehere E, Ravizzini G. Gallium-68 in medical imaging. Current radiopharmaceuticals. 2016 Dec 1;9(3):187-207.

 

  1. Velikyan I. 68Ga-based radiopharmaceuticals: production and application relationship. Molecules. 2015 Jul 16;20(7):12913-43.

 

  1. Kumar K. The current status of the production and supply of Gallium-68. Cancer biotherapy & radiopharmaceuticals. 2020 Apr 1;35(3):163-6.

 

  1. Velikyan I. 68Ga-based radiopharmaceuticals: production and application relationship. Molecules. 2015 Jul 16;20(7):12913-43.

 

  1. Nelson B.J, Andersson J.D, Wuest F, Spreckelmeyer S. Good practices for 68Ga radiopharmaceutical production. EJNMMI Radiopharmacy and Chemistry. 2022 Oct 22;7(1):27.

 

  1. Zolghadri S, Kakaei S, Yousefnia H, Bahrami-Samani A. Characterization of 68Ge/68Ga Generator and Quality Control of its Eluate. Journal of Nuclear Science and Technology. 2018;84:81-89 [In Persian].

 

  1. Roustaei H, Vosoughi H, Norouzbeigi N, Anvari K, Aryana K. Assessment of optimal uptake and acquisition time for [68Ga] Ga-pentixafor in patients with high-grade glioma. 2022;3298-3298.

 

  1. Roustaei H, Askari E, Norouzbeigi N, Vosoughi H, Aryana K. [68Ga] Ga-Pentixafor PET/CT uptake due to COVID-19 infection: An incidental finding in a patient with high-grade oligodendroglioma. Iranian Journal of Nuclear Medicine. 2023;31(1):101.

 

  1. Dadgar H, Seyedi Vafaee M, Norouzbeigi N, Jafari E, Gholamrezanezhad A, Assadi M. Dual-phase 68Ga-PSMA-11 PET/CT may increase the rate of detected lesions in prostate cancer patients. Urologia Journal. 2021 Nov;88(4):355-61.

 

  1. Rabie A, Yousefnia H, Zolghadri S, Shamsaei M, Jalilian A.R. Preparation, quality control and biodistribution study of 68Ga-BPAMD: Optimized production with an in-house 68Ge-68Ga generator. Iranian Journal of Nuclear Medicine. 2018 Jul 1;26(2):82-6.

 

  1. Aghanejad A, Jalilian A.R, Ardaneh K, Bolourinovin F, Yousefnia H, Samani A.B. Preparation and quality control of 68Ga-citrate for PET applications. Asia Oceania Journal of Nuclear Medicine and Biology. 2015;3(2):99.

 

  1. Fallahi B, Manafi-Farid R, Eftekhari M, Fard-Esfahani A, Emami-Ardekani A, Geramifar P, Akhlaghi M, Taheri A.P, Beiki D. Diagnostic efficiency of 68Ga-DOTATATE PET/CT as compared to 99mTc-Octreotide SPECT/CT and conventional morphologic modalities in neuroendocrine tumors. Asia Oceania Journal of Nuclear Medicine and Biology. 2019;7(2):129.

 

  1. Romero E, Martínez A, Oteo M, Ibañez M, Santos M, Morcillo M.Á. Development and long-term evaluation of a new 68Ge/68Ga generator based on nano-SnO2 for PET imaging. Scientific Reports. 2020 Jul 29;10(1):12756.

 

  1. Sriprapa T, Doungta T, Sakulsamart N, Taweewatthanasopon N, Madputeh L, Ragchana P, Sritongkul N, Tantawiroon M, Kongmuang S, Khiewvan B, Shiratori S. Evaluation of the Efficacy and Safety of the ITM 68Ge/68Ga Generator After its Recommended Shelf-life. Siriraj Medical Journal. 2023 Oct 1;75(10):752-8.

 

  1. Ocak M. 68Ge/68Ga Generators and Current Approach to Ga-68 Radiopharmaceuticals. Nukleer Tıp Seminerleri. 2023 Mar 1;9(1):31.

 

  1. Chakravarty R, Chakraborty S, Dash A, Pillai M.R. Detailed evaluation on the effect of metal ion impurities on complexation of generator eluted 68Ga with different bifunctional chelators. Nuclear Medicine and Biology. 2013 Feb 1;40(2):197-205.

 

  1. Šimeček J, Hermann P, Wester H.J, Notni J. How is 68Ga labeling of macrocyclic chelators influenced by metal ion contaminants in 68Ge/68Ga generator eluates? ChemMedChem. 2013 Jan;8(1):95-103.

 

  1. European Pharmacopoeia 10.0. Gallium (68Ga) chloride solution for radiolabelling. 2464.

Keywords

Pars-GalluGen generator
68Ge/68Ga generator
Quality control
Characterization
  1. Nelson B.J, Andersson J.D, Wuest F, Spreckelmeyer S. Good practices for 68Ga radiopharmaceutical production. EJNMMI Radiopharmacy and Chemistry. 2022 Dec;7(1):1-26.

 

  1. Rösch F. Past, present and future of 68Ge/68Ga generators. Applied Radiation and Isotopes. 2013 Jun 1;76:24-30.

 

  1. Jalilian A.R. An overview on Ga-68 radiopharmaceuticals for positron emission tomography applications. Iranian Journal of Nuclear Medicine. 2016;24(1):1.

 

  1. Roesch F. Maturation of a key resource–the germanium-68/gallium-68 generator: development and new insights. Current Radiopharmaceuticals. 2012 Jul 1;5(3):202-11.

 

  1. Meisenheimer M, Saenko Y, Eppard E. Gallium-68: Radiolabeling of Radiopharmaceuticals for PET Imaging—A Lot to Consider. Med Isot. 2019 Dec 23.

 

  1. Tsionou M.I, Knapp C.E, Foley C.A, Munteanu C.R, Cakebread A, Imberti C, Eykyn T.R, Young J.D, Paterson B.M, Blower P.J, Ma M.T. Comparison of macrocyclic and acyclic chelators for gallium-68 radiolabelling. RSC advances. 2017;7(78):49586-99.

 

  1. Lenzo N.P, Meyrick D, Turner J.H. Review of gallium-68 PSMA PET/CT imaging in the management of prostate cancer. Diagnostics. 2018 Feb 11;8(1):16.

 

  1. Rodnick M.E, Sollert C, Stark D, Clark M, Katsifis A, Hockley B.G, Parr D.C, Frigell J, Henderson B.D, Bruton L, Preshlock S. Synthesis of 68Ga-radiopharmaceuticals using both generator-derived and cyclotron-produced 68Ga as exemplified by [68Ga] Ga-PSMA-11 for prostate cancer PET imaging. Nature Protocols. 2022 Apr;17(4):980-1003.

 

  1. Okarvi S.M. Recent developments of prostate-specific membrane antigen (PSMA)-specific radiopharmaceuticals for precise imaging and therapy of prostate cancer: an overview. Clinical and Translational Imaging. 2019 Jun 1;7:189-208.

 

  1. Rodnick M.E, Sollert C, Stark D, Clark M, Katsifis A, Hockley B.G, Parr D.C, Frigell J, Henderson B.D, Abghari-Gerst M, Piert M.R. Cyclotron-based production of 68Ga, [68Ga] GaCl3, and [68Ga] Ga-PSMA-11 from a liquid target. EJNMMI Radiopharmacy and Chemistry. 2020 Dec;5:1-8.

 

  1. Hamed M.A, Basha M.A, Ahmed H, Obaya A.A, Afifi A.H, Abdelbary E.H. 68Ga-PSMA PET/CT in patients with rising prostatic-specific antigen after definitive treatment of prostate cancer: detection efficacy and diagnostic accuracy. Academic Radiology. 2019 Apr 1;26(4):450-60.

 

  1. Weitzer F, Pernthaler B, Plhak E, Riedl R, Aigner R.M. Diagnostic value of two-time point [68Ga] Ga-PSMA-11 PET/CT in the primary staging of untreated prostate cancer. Scientific Reports. 2023 May 22;13(1):8297.

 

  1. Maffey-Steffan J, Scarpa L, Svirydenka A, Nilica B, Mair C, Buxbaum S, Bektic J, Von Guggenberg E, Uprimny C, Horninger W, Virgolini I. The 68Ga/177Lu-theragnostic concept in PSMA-targeting of metastatic castration–resistant prostate cancer: impact of post-therapeutic whole-body scintigraphy in the follow-up. European journal of nuclear medicine and molecular imaging. 2020 Mar;47:695-712.

 

  1. Peters S.M, Hofferber R, Privé B.M, De Bakker M, Gotthardt M, Janssen M, De Lange F, Muselaers C.H, Mehra N, Witjes J.A, Costa P.F. [68Ga] Ga-PSMA-11 PET imaging as a predictor for absorbed doses in organs at risk and small lesions in [177Lu] Lu-PSMA-617 treatment. European Journal of Nuclear Medicine and Molecular Imaging. 2022 Mar 1:1-2.

 

  1. Zha Z, Choi S.R, Li L, Zhao R, Ploessl K, Yao X, Alexoff D, Zhu L, Kung H.F. New PSMA-Targeting Ligands: Transformation from Diagnosis (Ga-68) to Radionuclide Therapy (Lu-177). Journal of Medicinal Chemistry. 2022 Sep 14;65(19):13001-12.

 

  1. Sinnes J.P, Bauder-Wüst U, Schäfer M, Moon E.S, Kopka K, Rösch F. 68Ga, 44Sc and 177Lu-labeled AAZTA 5-PSMA-617: synthesis, radiolabeling, stability and cell binding compared to DOTA-PSMA-617 analogues. EJNMMI radiopharmacy and chemistry. 2020 Dec;5:1-1.

 

  1. Stenvall A, Gustafsson J, Larsson E, Roth D, Sundlöv A, Jönsson L, Hindorf C, Ohlsson T, Sjögreen Gleisner K. Relationships between uptake of [68Ga] Ga-DOTA-TATE and absorbed dose in [177Lu] Lu-DOTA-TATE therapy. EJNMMI research. 2022 Dec;12(1):1-5.

 

  1. Sainz-Esteban A, Prasad V, Schuchardt C, Zachert C, Carril J.M, Baum R.P. Comparison of sequential planar 177Lu-DOTA-TATE dosimetry scans with 68Ga-DOTA-TATE PET/CT images in patients with metastasized neuroendocrine tumours undergoing peptide receptor radionuclide therapy. European journal of nuclear medicine and molecular imaging. 2012 Mar;39:501-11.

 

  1. Hennrich U, Benešová M. [68Ga] Ga-DOTA-TOC: the first FDA-approved 68Ga-radiopharmaceutical for PET imaging. Pharmaceuticals. 2020 Mar 3;13(3):38.

 

  1. Breeman W.A, De Jong M, De Blois E, Bernard B.F, Konijnenberg M, Krenning E.P. Radiolabelling DOTA-peptides with 68Ga. European journal of nuclear medicine and molecular imaging. 2005 Apr;32:478-85.

 

  1. Kilian K. 68Ga-DOTA and analogs: Current status and future perspectives. Reports of Practical Oncology & Radiotherapy. 2014 May 1;19:S13-21.

 

  1. Fani M, Mansi R, Nicolas G.P, Wild D. Radiolabeled somatostatin analogs—a continuously evolving class of radiopharmaceuticals. Cancers. 2022 Feb 24;14(5):1172.

 

  1. Martiniova L, Palatis L.D, Etchebehere E, Ravizzini G. Gallium-68 in medical imaging. Current radiopharmaceuticals. 2016 Dec 1;9(3):187-207.

 

  1. Velikyan I. 68Ga-based radiopharmaceuticals: production and application relationship. Molecules. 2015 Jul 16;20(7):12913-43.

 

  1. Kumar K. The current status of the production and supply of Gallium-68. Cancer biotherapy & radiopharmaceuticals. 2020 Apr 1;35(3):163-6.

 

  1. Velikyan I. 68Ga-based radiopharmaceuticals: production and application relationship. Molecules. 2015 Jul 16;20(7):12913-43.

 

  1. Nelson B.J, Andersson J.D, Wuest F, Spreckelmeyer S. Good practices for 68Ga radiopharmaceutical production. EJNMMI Radiopharmacy and Chemistry. 2022 Oct 22;7(1):27.

 

  1. Zolghadri S, Kakaei S, Yousefnia H, Bahrami-Samani A. Characterization of 68Ge/68Ga Generator and Quality Control of its Eluate. Journal of Nuclear Science and Technology. 2018;84:81-89 [In Persian].

 

  1. Roustaei H, Vosoughi H, Norouzbeigi N, Anvari K, Aryana K. Assessment of optimal uptake and acquisition time for [68Ga] Ga-pentixafor in patients with high-grade glioma. 2022;3298-3298.

 

  1. Roustaei H, Askari E, Norouzbeigi N, Vosoughi H, Aryana K. [68Ga] Ga-Pentixafor PET/CT uptake due to COVID-19 infection: An incidental finding in a patient with high-grade oligodendroglioma. Iranian Journal of Nuclear Medicine. 2023;31(1):101.

 

  1. Dadgar H, Seyedi Vafaee M, Norouzbeigi N, Jafari E, Gholamrezanezhad A, Assadi M. Dual-phase 68Ga-PSMA-11 PET/CT may increase the rate of detected lesions in prostate cancer patients. Urologia Journal. 2021 Nov;88(4):355-61.

 

  1. Rabie A, Yousefnia H, Zolghadri S, Shamsaei M, Jalilian A.R. Preparation, quality control and biodistribution study of 68Ga-BPAMD: Optimized production with an in-house 68Ge-68Ga generator. Iranian Journal of Nuclear Medicine. 2018 Jul 1;26(2):82-6.

 

  1. Aghanejad A, Jalilian A.R, Ardaneh K, Bolourinovin F, Yousefnia H, Samani A.B. Preparation and quality control of 68Ga-citrate for PET applications. Asia Oceania Journal of Nuclear Medicine and Biology. 2015;3(2):99.

 

  1. Fallahi B, Manafi-Farid R, Eftekhari M, Fard-Esfahani A, Emami-Ardekani A, Geramifar P, Akhlaghi M, Taheri A.P, Beiki D. Diagnostic efficiency of 68Ga-DOTATATE PET/CT as compared to 99mTc-Octreotide SPECT/CT and conventional morphologic modalities in neuroendocrine tumors. Asia Oceania Journal of Nuclear Medicine and Biology. 2019;7(2):129.

 

  1. Romero E, Martínez A, Oteo M, Ibañez M, Santos M, Morcillo M.Á. Development and long-term evaluation of a new 68Ge/68Ga generator based on nano-SnO2 for PET imaging. Scientific Reports. 2020 Jul 29;10(1):12756.

 

  1. Sriprapa T, Doungta T, Sakulsamart N, Taweewatthanasopon N, Madputeh L, Ragchana P, Sritongkul N, Tantawiroon M, Kongmuang S, Khiewvan B, Shiratori S. Evaluation of the Efficacy and Safety of the ITM 68Ge/68Ga Generator After its Recommended Shelf-life. Siriraj Medical Journal. 2023 Oct 1;75(10):752-8.

 

  1. Ocak M. 68Ge/68Ga Generators and Current Approach to Ga-68 Radiopharmaceuticals. Nukleer Tıp Seminerleri. 2023 Mar 1;9(1):31.

 

  1. Chakravarty R, Chakraborty S, Dash A, Pillai M.R. Detailed evaluation on the effect of metal ion impurities on complexation of generator eluted 68Ga with different bifunctional chelators. Nuclear Medicine and Biology. 2013 Feb 1;40(2):197-205.

 

  1. Šimeček J, Hermann P, Wester H.J, Notni J. How is 68Ga labeling of macrocyclic chelators influenced by metal ion contaminants in 68Ge/68Ga generator eluates? ChemMedChem. 2013 Jan;8(1):95-103.

 

  1. European Pharmacopoeia 10.0. Gallium (68Ga) chloride solution for radiolabelling. 2464.

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